Clinical trials are systematic investigations conducted on human subjects (either patients or healthy subjects) to evaluate the efficacy, safety, and pharmacological properties such as absorption, distribution, metabolism, and excretion of investigational drugs or medical devices (1). Healthy subjects play an indispensable role in this process. A healthy subject refers to an individual with no known diseases or abnormalities relevant to the study, with physiological and laboratory parameters within normal ranges, free from interfering factors, who volunteers to participate and does not seek therapeutic benefit. The development and approval of any new drug depend critically on their participation. Unlike patient volunteers, healthy subjects do not suffer from the condition the drug is intended to treat. They undertake potential unknown risks without the prospect of therapeutic benefit, making their willingness to participate a central ethical and practical concern (2, 3). Therefore, understanding the factors that influence the willingness of healthy individuals to take part in clinical trials and conducting targeted educational initiatives is essential for enhancing trust and engagement.

The willingness of healthy subjects to participate directly impacts the speed and quality of trial recruitment, which in turn affects both the timeline and cost of clinical development (4). However, participant recruitment remains a major challenge in clinical research. The decision to enroll is influenced by a complex array of factors. While substantial research has focused on factors affecting patients’ willingness to participate, studies specifically addressing healthy volunteers remain relatively limited. Existing research, both internationally and domestically, has identified several influential factors, including inadequate publicity of clinical trial information (5), insufficient communication from research staff (6), as well as demographic variables such as gender and educational level (7), and trust in medical staff (8).

Despite these efforts, there remains a notable lack of empirical research within the socio-cultural context of China examining the willingness of healthy subjects to participate in clinical trials. In particular, comprehensive analyses that integrate multiple dimensions such as socio-demographic characteristics, levels of awareness of clinical trials, and understanding of ethical oversight are still scarce. To address this gap, this study employs a cross-sectional survey design within the Chinese context, specifically targeting healthy subjects – a group often underrepresented in clinical trial participation research. By recruiting individuals from a health examination center and community residents, the study aims to assess willingness to participate and identify key influencing factors unique to this population. The findings are expected to contribute to the theoretical framework of clinical trial recruitment and offer practical insights for improving recruitment efficiency, safeguarding participants’ rights, and enhancing the overall quality of clinical research.

Clinical drug trials represent a critical phase in pharmaceutical development, and healthy subjects serve as one of the essential participants in these studies. Understanding the willingness of potential healthy subjects to participate, clarifying the factors influencing their willingness, and implementing targeted measures to enhance their participation are crucial for improving clinical trial enrollment rates.

This survey found that the willingness of potential healthy subjects to participate in clinical trials was 53.66%, which is higher than the results reported by Chu et al. (9) in South Korea, significantly lower than the findings of Almutairi et al. (10) and Bouida et al. (11), and similar to the results of Raheja et al. (12) The considerable variation in participation rates across different regions and countries may be related to factors such as fear of investigational drugs or devices, lack of time, as well as social customs and cultural differences. Therefore, conducting region-specific investigations is essential to better enhance the participation rate of healthy subjects in clinical trials.

Unlike patient subjects who are motivated by potential clinical benefits, healthy subjects generally exhibit lower willingness to participate in trials since they do not seek therapeutic gains (13–15). Currently, most healthy subjects participating in clinical trials are individuals in need of financial compensation and with ample spare time, such as the unemployed individuals not actively seeking work or university students. Furthermore, the willingness of healthy subjects to participate is also influenced by the type of trial; for example, willingness is significantly lower for trials involving invasive procedures or those with serious side effects compared to non-invasive studies (16). Although this study did not differentiate among types of potential trial projects, practical experience has shown that participation rates tend to be higher for low-risk studies, such as dermal tests and other non-invasive, non-oral drug administration trials.

Our findings indicate that place of residence, employment status, and level of understanding of clinical trials serve as significant predictors of participation willingness. The results demonstrated that urban healthy subjects exhibited a significantly higher willingness to participate in clinical trials compared to those from rural areas. This discrepancy may be attributed to the more accessible dissemination of clinical trial knowledge and health education in urban settings, where individuals are more likely to be exposed to relevant information, leading to greater awareness and understanding of clinical trials (17). Complementarily, urban areas are typically endowed with more abundant medical resources and a higher concentration of clinical trial institutions, which enhances participation convenience while reducing associated time and transportation costs. Beyond structural advantages, urban populations often exhibit more open attitudes toward novel experiences and innovations, translating to a greater propensity to engage in clinical trials.

Furthermore, this urban–rural disparity is underpinned by structural socioeconomic determinants: urban populations generally demonstrate higher aggregate health literacy and educational attainment, which facilitate the comprehension of trial protocols and nuanced risk benefit assessments. Concurrently, differential access to digital information and technology – often substantially limited in rural settings – may constrain awareness of trial opportunities and reinforce informational inequities. Finally, variations in institutional trust and social capital between urban and rural communities could modulate perceptions of safety and willingness to engage in formal clinical research endeavors.

Our study revealed that unemployed individuals not actively seeking work healthy subjects demonstrated a higher willingness to participate compared to their employed counterparts, which contrasts with the findings reported by Rein-Hedin et al. (2) This discrepancy may be explained by the fact that most unemployed individuals not actively seeking work individuals lack a stable income and have more flexible schedules, enabling them to accommodate the time requirements of clinical trials more easily and reducing conflicts arising from employment obligations. Furthermore, some unemployed individuals not actively seeking work individuals may experience financial pressures, making the financial compensation offered for trial participation a motivating factor (15). Consequently, they may be more inclined to accept potential risks associated with clinical trials, thereby increasing their willingness to participate. This study found no evidence that healthy subjects actively seeking employment exhibited a higher willingness to participate. While both unemployed individuals not actively seeking work and those actively seeking employment lack permanent jobs, healthy subjects in the job-seeking group typically prioritize job-seeking as their primary focus and allocate their time and energy accordingly. They may be concerned that participating in clinical trials could interfere with their job search process, which could contribute to their lower willingness to participate.

The present study found that healthy subjects with a moderate level of awareness of clinical trials showed a significantly higher willingness to participate compared to those with lower levels of understanding. This is inconsistent with the research results of Elshammaa et al. (18), which may be related to cultural customs. When individuals have a clearer understanding of the objectives, procedures, potential risks, and benefits of clinical trials, they are better equipped to conduct a rational assessment of the advantages and disadvantages of involvement, thereby increasing their willingness to enroll. In contrast, those with limited awareness are more likely to hold misconceptions or concerns, such as fears about potential physical harm from investigational drugs or doubts regarding the safety of trial procedures, which may diminish their inclination to participate. It is noteworthy that while descriptive data suggested an association between high understanding and willingness, it did not emerge as a significant independent predictor in the multivariate model. This may indicate a non-linear relationship, where moderate knowledge optimally reduces uncertainty and fosters willingness, whereas high understanding may involve more complex, conditional decision-making that does not uniformly translate into higher participation intent.

Our study revealed a counterintuitive finding: healthy subjects aware of the functions of an ethics committee exhibited a lower willingness to participate, which contrasts with some prior studies conducted primarily in patient populations (19). This discrepancy may be explained by the unique perspective of healthy volunteers, who undertake risk without therapeutic benefit. For them, knowledge of ethical oversight might not merely signify protection, but also heighten the salience of potential risks and procedural burdens, leading to more cautious assessment. Furthermore, awareness could correlate with greater scrutiny of the informed consent process and the real-world independence of ethics committees, potentially uncovering reservations about their effectiveness in practice (20). This finding may also reflect a specific socio-cultural context where institutional trust is nuanced. Therefore, while ethical oversight is fundamental, simply increasing awareness of its existence may not be sufficient to bolster willingness among healthy subjects; instead, demonstrating its tangible effectiveness and commitment to participant welfare through transparent communication might be more critical.

Existing research suggests that younger (21), those with a history of clinical trial participation (22, 23), female (24), subjects with lower income levels (3), and those receiving recommendations from healthcare providers (8) are generally more inclined to participate in clinical trials. However, our study did not identify significant differences between the groups regarding these factors. This discrepancy may be attributable to the relatively small sample size and the narrow age distribution of the participants. Future multi-center studies with larger sample sizes are needed to better elucidate the influence of these factors on the willingness of healthy subjects to participate in clinical trials.

Although this study comprehensively discussed the factors affecting healthy subjects’ willingness to participate in clinical trials, it has several limitations. First, the cross-sectional design precludes causal inferences regarding the factors associated with willingness to participate. Second, the use of convenience sampling from a single geographic region limits the generalizability of the findings. Third, self-reported data are subject to social desirability and recall biases. Fourth, the assessment of willingness did not differentiate between types of clinical trials (e.g., invasive vs. non-invasive), which may influence real-world decisions. Finally, the sample size and concentrated age range may have limited the detection of some associations.

Despite these limitations, the study provides initial insights into an under-researched population in the Chinese context. Future studies with longitudinal designs, probability sampling, and differentiation of trial types are warranted to enhance causal inference and generalizability.

This study systematically elucidated the epidemiological characteristics of healthy subjects and the factors influencing their willingness to participate in clinical trials. The results indicated that urban residents, unemployed individuals not actively seeking work, and those with a moderate level of understanding of clinical trials exhibited a higher willingness to participate. In contrast, subjects unaware of the functions of an ethics committee showed lower willingness. These findings refine the characteristic profile of potential healthy subjects and provide a direct basis for developing targeted recruitment strategies, such as strengthening trial-related education in medically underserved communities and adopting differentiated communication to address specific information and motivation gaps.

Conducting comparative studies across different socioeconomic and cultural contexts, delving into the psychological mechanisms behind healthy subjects’ decisions to participate in clinical trials, and systematically designing and evaluating targeted recruitment programs represent critical steps for translating these insights into practice. Implementing these strategies may increase willingness among healthy subjects to engage in clinical trials, alleviate recruitment challenges, ensure the smooth progress of clinical trials, and ultimately promote the healthy development of pharmaceutical research.