Comparison of the characteristics of healthy volunteers participating in Phase 1 clinical trials in Korea and Japan

Abstract

This paper aims to elucidate the characteristics of healthy volunteers in Korea and Japan. Clinical trials can be divided into Phases 1 through 4 based on the stage of research. Unlike other phase, Phase 1 trials administer new drugs to healthy volunteers. Although Phase 1 trials are the first stage of drug administration to humans, without therapeutic purposes. Healthy volunteers must have no history of diseases that could affect the study and must have normal physical measurements. They are also defined as individuals who understand the study and can voluntarily consent to participate. Also, it is crucial to conduct them ethically. To date, there has been insufficient research on the Phase 1 clinical trials in Korea and Japan, and in-depth analysis of the perceptions and the motivations. This study enrolled healthy volunteers in Korea and Japan to conduct surveys related to demographic information and their perception.

INTRODUCTION

This paper aims to examine the characteristics of Phase 1 clinical trials conducted in Korea and Japan, focusing on the profiles of healthy volunteers who participate in these studies. The research will explore the volunteers’ perceptions and attitudes towards their involvement in these trials, shedding light on the key factors influencing their decision to participate. Clinical trials are experimental studies conducted on humans to validate the efficacy and safety of new treatments, including new drugs. This represents an intermediate stage in the drug development process, serving to confirm whether the results from laboratory studies, including preclinical trials, are applicable to humans. Clinical trials are a necessary step that must be completed before a new drug can be used to treat human diseases. These trials are classified into 4 phases (Phase 1 through Phase 4), each representing a different stage of the study. Throughout all phases, the safety of participants must be a primary consideration. Unlike Phase 2, 3, and 4 trials, which involve patients with the condition being studied, Phase 1 trials are designed to administer new drugs to a relatively limited number of healthy volunteers (typically 20–80, sometimes fewer than 20) based on preclinical data from animal studies. These studies focus on determining pharmacokinetics, pharmacodynamics, side effects, and safe dosage range. While Phase 1 trials are the first step in drug administration to humans, they do not have therapeutic purposes.

Clinical trials are conducted on human subjects, making it crucial to perform them ethically, with the utmost consideration for the safety and welfare of participants. Phase 1 clinical trials involve administering a new drug to healthy volunteers to evaluate its pharmacological effects in the human body and assess its safety. Healthy volunteers participating in Phase 1 trials should have no history of diseases that could affect the trial, and their physical measurements should fall within normal ranges. They are also defined as individuals who fully understand the study and can voluntarily consent to participate. Healthy volunteers in Phase I trials are exposed to study-drug risks without the possibility of direct medical benefit, as such trials are designed primarily to test the safety and tolerability of investigational pharmaceuticals [1]. Participants in Phase 1 clinical trials do not gain therapeutic benefits and may experience unanticipated side effects. The motivations for participating in Phase 1 clinical trials among healthy volunteers differ from those of patients participating in clinical trials. It is generally perceived that financial reward is one of the primary motivations for healthy volunteers to participate in clinical trials. In studies conducted with healthy volunteers in Korea, the primary purpose of participation for most volunteers was financial compensation [2]. The majority rated consideration of risks as more important to their enrollment decision than the amount of money, despite reporting that their primary motivation was financial. Risk, time, money, the competence and friendliness of research staff, and contributing to medical research were important factors influencing enrollment decisions for most participants [3]. In another study, the motivations were varied and not solely centered on financial gains, with altruism reported as an advantage of participation and inconvenience most often cited as a disadvantage [4].

In 2023, a total of 783 clinical trials were conducted in South Korea, placing the country in fourth place globally. According to the Ministry of Food and Drug Safety, South Korea ranked fourth globally in the number of clinical trial registrations, with Seoul leading in ‘clinical trials by city’ and South Korea ranking third for ‘clinical trials in a single country’ [5].

The number of Phase 1 clinical trials conducted in South Korea has increased from 269 in 2022 to 307 in 2023, surpassing the 107 Phase 2 trials and 237 Phase 3 trials conducted in the same year [6]. As the number of Phase 1 clinical trials continues to rise in our country, it is expected that the number of healthy volunteers who have experienced Phase 1 clinical trials will also increase.

Reflecting the expanding scale of clinical trials in South Korea, particularly in Seoul, there has been a growing interest in Phase 1 clinical trials and healthy volunteers participating in these trials. Various media outlets have been reporting on the social perceptions of healthy volunteers [7]. Additionally, when examining the clinical trial registration status in Japan, the cumulative number of studies reached 4,910 in 2017, making it one of the highest in East Asia, following China and South Korea [8]. Despite the active conduct of clinical trials in both Korea and Japan, there have been no prior studies that identify the characteristics of healthy volunteers participating in Phase 1 clinical trials or that explore the differences between the 2 countries. This study aims to understand the motivations and perceptions of healthy volunteers participating in Phase 1 clinical trials in Korea and Japan, as well as to identify the characteristics of these healthy volunteers.

Specifically, this study first aimed to identify the demographic characteristics of healthy volunteers participating in Phase 1 clinical trials and to explore their motivations and perceptions regarding participation. It examined whether demographic factors influence the decision to participate in a study and whether perceptions and attitudes toward the study are affected by the individual characteristics of the healthy volunteers.

Additionally, the study compared the information provided to healthy volunteers during the informed consent process with the information delivered by investigators during the same process. By examining the experiences of healthy volunteers, the study explored the progression of clinical trials and considered potential ethical issues that may arise. In other words, the characteristics of currently ongoing clinical trials can be indirectly verified through the experiences and perceptions of healthy volunteers, allowing for an evaluation of the ethical aspects involved.

METHODS

Study design

To examine the demographic characteristics of healthy volunteers participating in Phase 1 clinical trials and identify the factors influencing their decision to participate, a survey method was employed. For the statistical analysis of the survey results, this study included more than 100 healthy volunteers. To ensure a representative sample, the focus was on healthy volunteers who had previously completed participation in clinical trials. The survey was administered to individuals with at least one prior experience in such studies. A survey was conducted with healthy volunteers who participated in Phase 1 clinical trials at the Seoul National University Hospital Clinical Trial Center between June and August 2013. Prior to the study, Institutional Review Board (IRB) approval was obtained (IRB approval number: 1304-016-477), and a total of 121 healthy volunteers completed the survey. Simultaneously, a similar survey was administered at the Kitasato University Hospital Clinical Trial Center in Japan, involving 135 healthy volunteers using the same questionnaire. IRB approval was obtained (IRB approval number: B11-33) A research agreement was established to facilitate the mutual utilization of the findings from both Seoul Hospital study and the results from Kitasato Hospital.

Data collection

Before conducting the survey for this study, participants were provided with sufficient information to make an informed decision about their participation, and consent was obtained. The survey was administered after the healthy volunteers completed their participation in the Phase 1 clinical trials at the clinical trial center and was conducted anonymously. Participation in the survey was entirely voluntary. The survey was divided into 2 main sections: Section 1 collected demographic background information about the healthy volunteers, while Section 2 explored the participants’ experiences, motivations, and perceptions regarding clinical trial participation. The questionnaire used in the study is included as a Supplementary Data 1.

Data analysis

Data entry for the survey was performed using Microsoft Office Excel (Microsoft, Redmond, WA, USA), and the results were summarized using frequencies and percentages. Additionally, the findings from the Seoul National University Hospital were compared with those from Kitasato University Hospital in Japan. A bar graph was used to present the comparison between the 2 countries. To analyze differences in motivation and satisfaction between groups, the Mann–Whitney test (for 2 groups) and the Kruskal–Wallis test (for 3 groups) were employed, as the data did not meet the assumption of homogeneity of variance, and p-values < 0.05 were considered statistically significant. To perform parametric tests, the assumptions of normality and homogeneity of variance must be satisfied; therefore, preliminary tests for these assumptions were conducted. The analysis indicated that the data in this study did not meet the assumption of homogeneity of variance, and consequently, non-parametric tests were employed. Further analyses were conducted to confirm the survey results, and to identify correlations between each of the variables.

RESULTS

Survey and interview results between Korea and Japan

We compare the survey results from South Korea and Japan. As shown in Table 1, there are significant differences between the 2 countries regarding age, occupation, income, and household structure. In South Korea, a higher proportion of participants was students, part-time workers, and unemployed individuals, whereas Japan had a significantly higher proportion of full-time employees. Regarding income, South Korea had a higher proportion of average-income individuals (earning over 2.4 million KRW) compared to Japan. As of 2014, according to data provided by the Ministry of Employment and Labor, the average monthly wage of workers was approximately 2,022,000 KRW for those aged 20–24, and 2,685,000 KRW for those aged 25–29. Therefore, 2,400,000 KRW was designated as the average wage [9]. Conversely, participants in Japan generally reported lower monthly incomes. However, this higher reported income in South Korea may be influenced by the significant proportion of students and individuals living in family-owned homes. If the survey had focused on individual income rather than household income, the results might have been different. When comparing data from Korea and Japan, we chose to use the U.S. dollar as the unit of measurement, as it serves as an international standard, rather than using the currency of either country.

Table 1. Comparison of demographic characteristics of healthy volunteers participating in Phase 1 clinical trials in Korea and Japan.

Characteristics		Korea	Japan	p-value
Sex (male/female)		121 (118/3)	135 (135/0)	0.104
Age (mean ± SD)		28.66 ± 5.98	27.13 ± 5.54	0.002*
Marriage				0.753
	Single	117 (96.7)	129 (95.6)
	Married/cohabit/divorce/bereaved	4 (3.3)	6 (4.4)
Children				0.397
	0	89 (96.7)	133 (98.5)
	1	0 (0)	0 (0)
	2	3 (3.3)	2 (1.5)
Employed status				0.012*
	Student	63 (52.5)	56 (41.8)
	Full-time	9 (7.5)	21 (15.7)
	Part-time	20 (16.7)	37 (27.6)
	Unemployed	28 (23.3)	20 (14.9)
Education				0.133
	Graduate high school	13 (10.8)	27 (20)
	Under-graduate	52 (43.3)	53 (39.3)
	Graduate college/university	55 (45.8)	55 (40.7)
Monthly income				0.001*
	Under $1,000	33 (28.0)	59 (44.0)
	$1,000–$2,000	33 (28.0)	44 (32.8)
	$2,000–$3,000	25 (21.2)	25 (18.7)
	$3,000–$4,000	9 (7.6)	4 (3.0)
	Over $4,000	18 (15.3)	2 (1.5)
House				0.001*
	Family-owned	66 (55.0)	47 (34.8)
	My own house	11 (9.2)	4 (3.0)
	Rent house	36 (30.0)	77 (57.0)
	Dormitory	1 (0.8)	0 (0.0)
	Etc.	6 (5.0)	7 (5.2)

Values represent number (%) or mean ± standard deviation. To analyze differences in motivation and satisfaction between groups, the Mann–Whitney test (for 2 groups) and the Kruskal–Wallis test (for 3 groups) were employed, and p-values < 0.05 were considered statistically significant.

SD, standard deviation.

^*p ≤ 0.05.

As shown in Table 2, a higher percentage of respondents in Japan reported participating in clinical trials for the first time, whereas in South Korea, 24.2% of respondents indicated that they had participated in 3 or more trials, indicating a significant difference between the 2 countries. Furthermore, when asked if they would participate in the study without financial reward, 91.4% of respondents in South Korea and 83.7% of respondents in Japan said they would not participate, indicating that there was no notable difference.

Table 2. Comparison of participation based on clinical trial experience.

Characteristics			Korea	Japan	p-value
Comparison of participation based on clinical trial experience and financial reward
	No. of participation				0.001***
		1 time	43 (35.8)	86 (63.7)
		2 times	25 (20.8)	30 (22.2)
		3 times	23 (19.2)	7 (5.2)
		More than 3 times	29 (24.2)	12 (8.9)
	Total		120	135
	Would you participate even if you could not receive financial reward?				0.069
		Yes, I would.	2 (1.7)	4 (3.0)
		I am not sure.	8 (6.7)	18 (13.3)
		No, I would not.	106 (91.4)	113 (83.7)
		Others	4 (3.4)	0
	Total		120	135
Reactions of others to participants’ decision to join a clinical trial
	How did the people you consulted react to your decision to participate in the clinical trial?				0.887
		Yes	35 (29.2)	38 (28.4)
		No	85 (70.8)	96 (71.6)
	Total		120	134
When they recommended you should not participate, did they have any experience of participating in clinical trials before?
	How did they react regarding your participation?				0.743
		Almost all said “yes.”	4 (10.8)	8 (21.6)
		Some said “yes,” but some said “no.”	26 (70.3)	23 (62.2)
		Almost all said “no.”	6 (16.7)	5 (13.9)
		All said “no.”	0	0
		Others	1 (2.7)	1 (2.7)
	Total		37	37
	When they recommended you should not participate, did they have any experience of participating in clinical trials before?				0.482
		All ex-participants	1 (3.8)	0
		Some ex-participants	5 (19.2)	4 (14.3)
		Not ex-participants	20 (76.9)	22 (78.6)
		I am not sure.	0	2 (7.1)
		Others	0	0
	Total		26	28
Comparison of satisfaction with financial reward between Korea and Japan
	Financial reward				0.246
		Satisfactory/good	52 (43.3)	70 (53.0)
		Reasonable	61 (50.8)	53 (40.1)
		Unsatisfactory/bad	7 (5.8)	8 (6.1)
		Others	0	1 (0.8)
	Total		120	132
How do you consider the information provided for your consent prior to participation?
	How do you consider the information provided for your consent prior to participation?				0.678
		More than enough	5 (4.1)	5 (3.8)
		Enough	101 (83.5)	104 (78.2)
		Not enough	14 (11.6)	20 (15.0)
		Others	1 (0.8)	4 (3.0)
	Total		121	133
	Was your actual experience in this trial different from the information provided before your participation?				0.016*
		Yes, it was different.	0 (0)	7 (5.2)
		No, it was not different.	119 (100)	128 (94.8)
	Total		119	135
Comparison of possibility of serious side effects and future willingness to participate and willingness to recommend participation
	How did you feel about the possibility of an occurrence of a serious complication during this trial?				0.001***
		I never feel that possibility.	84 (70.0)	128 (94.8)
		Occasionally, I feel that possibility.	35 (29.2)	7 (5.2)
		I feel that possibility for significant period of time.	0	0
		Others	1 (0.8)	0
	Total		120	135
	Would you participate in a healthy volunteer experiment again?				0.069
		Yes, I would.	88 (72.7)	86 (63.7)
		I am not sure.	33 (27.3)	42 (31.1)
		No, I would not.	0	2 (1.5)
		Others	0	5 (3.7)
	Total		121	135
	Would you recommend your relatives and friends to participate in a healthy volunteer experiment?				0.001***
		Yes, I would.	57 (47.1)	33 (24.6)
		I am not sure.	39 (32.2)	55 (41.0)
		No, I would not.	22 (18.2)	42 (31.3)
		Others	3 (2.5)	4 (3.0)
	Total		121	134

Values represent number (%) or mean ± standard deviation. To analyze differences in motivation and satisfaction between groups, the Mann–Whitney test (for 2 groups) and the Kruskal–Wallis test (for 3 groups) were employed, and p-values < 0.05 were considered statistically significant.

^*p ≤ 0.05, ^***p ≤ 0.001.

In response to the question about motivations for participating in clinical trials, as shown in Fig. 1, the categories “contribution to the progress of medicine” (p < 0.001), “free health check-up” (p = 0.031), and “curiosity about clinical trials” (p < 0.001) were significantly higher among Japanese participants compared to their Korean counterparts. The higher score for curiosity about clinical trials among Japanese respondents is likely due to a greater number of healthy volunteers participating for the first time. In contrast, Korea has a higher proportion of individuals who have participated in clinical trials multiple times. Both countries reported the lowest scores for the category “contribution to the advancement of medicine,” indicating a relatively low level of altruistic motivation for participating in clinical trials. No significant difference was observed between the 2 countries regarding financial reward. In both countries, financial compensation was the primary motivation for research participation; however, curiosity and free health checkups were reported significantly more often in Japan than in Korea. The higher level of curiosity among Japanese healthy volunteers may be explained by the fact that a larger proportion of them were first-time participants in clinical trials.

Figure 1. Experience participating in clinical trials. (A) Motives of participating in clinical trials; (B) Ways of acquiring information; (C) Someone whose opinion you ask; (D) Reasons for opposition; (E) Factors for evaluating the relevance of financial reward; (F) Important information for participation decision; (G) Level of satisfaction; (H) Level of inconvenience. To analyze differences in motivation and satisfaction between groups, the Mann–Whitney test (for 2 groups) and the Kruskal–Wallis test (for 3 groups) were employed, and p-values < 0.05 were considered statistically significant.

^*p ≤ 0.05, ^**p ≤ 0.01, ^***p ≤ 0.001.

Both countries identified the “Website” as the most prominent source of information regarding clinical trials. Additionally, there was no significant difference between the 2 countries in terms of whether individuals sought opinions from others before deciding to participate (Table 2).

In response to the question about whom they consulted regarding participation in clinical trials, Fig. 1 indicates that Japanese respondents were more likely to seek advice from their family. In contrast, both countries reported that consulting friends was the most common practice.

As shown in Table 2, despite these differences in sources of advice, there was no significant difference between Korea and Japan regarding the likelihood of encountering opposition when consulting others. Notably, only about 16.7% in Korea, 13.9% in Japan reported facing opposition. which is an intriguing finding. Although public perceptions of clinical trials are generally negative, the proportion of those who explicitly oppose them can be considered relatively low [10].

Furthermore, there was no significant difference between the 2 countries concerning the clinical trial participation experience of those who opposed participation. The primary reason for opposition, as illustrated in Fig. 1, was concern about “risks,” which was the most frequently cited reason in both countries.

In the satisfaction survey regarding financial reward, most respondents reported being “satisfied” or “reasonable,” with no difference observed between respondents in Korea and Japan (Table 2).

Among the factors evaluating the adequacy of financial reward, Japanese participants rated “risk in health from adverse events to investigational drug” (p = 0.007) and “length of participating period in clinical trial” (p = 0.001) significantly higher than their Korean participants. There was no notable difference between Japanese and Korean participants regarding the sufficiency of the information provided. However, when asked about discrepancies between their actual experience and what was reported, all respondents in Korea indicated no difference, while 7 respondents in Japan reported a discrepancy. This difference is statistically significant (p = 0.016) (Table 2).

Regarding the importance of clinical trial information to participants, as shown in Fig. 1, Japanese healthy volunteers rated the following aspects significantly higher than their Korean counterparts: “drug and adverse events” (p = 0.002), “frequency of visits” (p = 0.021), and “procedures and examination” (p = 0.002). However, there was no significant difference between the 2 countries concerning the “financial reward” (p = 0.739). This result suggests that Japanese participants may be more sensitive and attentive to information and procedures compared to Korean participants. This heightened sensitivity may be attributed to the higher proportion of Japanese clinical trial participants who have no previous research experience.

In comparing satisfaction with the clinical trial process, Korean healthy volunteers reported significantly higher satisfaction than their Japanese counterparts in 4 areas: “facilities for rest and convenience” (p < 0.001), “measures to protect healthy volunteers” (p = 0.009), “facilities and equipment for research” (p < 0.001), and “communication with the research team” (p = 0.007). This disparity may be due to the characteristics of the institutions where the surveys were conducted. For example, feedback from interviews and detailed discussions suggested that the Clinical Trials Center at Seoul National University Hospital offered higher satisfaction with its facilities compared to other institutions. In contrast, the survey conducted at Kitasato University Hospital in Japan indicated lower satisfaction levels, particularly when compared to other private institutions in Japan with superior facilities. Both Korean and Japanese participants expressed significant dissatisfaction with “blood sampling.” A notable difference between the 2 countries was observed only in the “facilities for rest and convenience” category (p = 0.012).

As shown in Table 2, a significantly higher percentage of participants in Japan (94.8%) did not consider the possibility of serious adverse events compared to Korea (70%) (p ≤ 0.001). While previous results indicated that Japanese participants were more sensitive to information and risks, their concern about potential adverse effects was lower than that of Korean participants.

There was little difference between Korea and Japan regarding participants' willingness to consider participating in clinical trials again. However, a higher percentage of participants in Korea expressed a willingness to rejoin. When asked whether they would recommend participation to others, approximately 24.6% of Japanese participants and 47.1% of Korean participants responded “yes,” indicating a notable difference. Specifically, 72.7% of Korean participants said they would re-participate, while about 47.1% would recommend participation to others. In contrast, 63.7% of Japanese participants expressed a willingness to re-participate, but only 24.6% would recommend it to others. This suggests that while participants may feel confident about their own involvement in clinical trials, they are less inclined to recommend it to others, potentially due to perceived responsibilities and the potential negative impact on others. This could reflect a broader societal negative perception of clinical trials.

As a result of comparing the speed of participant enrollment by phase, the clinical trials conducted by the top 10 Japanese pharmaceutical companies showed a significantly faster enrollment speed in Phase 1 trials with healthy volunteers and oncology patients than those conducted by the global top 10 pharmaceutical companies [11]. This may act as a discouraging factor in recommending participation to others. Furthermore, a comparative study on individualism across Korea, China, Japan, and the Netherlands found that individualism was strongest in the Netherlands and Japan, with China and Korea showing lower levels. Japan, in particular, exhibited the highest individualism in terms of ‘indifference to others’ [12]. Emancipation refers to the process by which an individual or group frees itself from external constraints, control, or authority. In cultural psychology and the social sciences, emancipation is regarded as an indicator of autonomy and the strengthening of self-determination, and it is closely associated with individualistic values. A study examining autonomy and emancipation in Korea and Japan found that levels of autonomy were higher in Japan [13]. The strong autonomy and emancipation in Japan may partly explain why healthy volunteers are less inclined to encourage others to participate in clinical trials.

In both countries, the majority of respondents had participated in clinical trials at least twice. When asked about any negative aspects of their clinical trial experiences, volunteers from both Korea and Japan highlighted difficulties with blood collection and discomfort with the facilities. Despite these issues, volunteers in both countries generally expressed a positive attitude toward future participation in research. They emphasized the importance of study duration and scheduling. While recommending clinical trials to others was often viewed as simply providing information, the reluctance to recommend them was primarily attributed to concerns about the risks involved in human trials and societal perceptions. Responses from both countries were similar in this regard.

Despite differences in the recruitment systems for healthy volunteers in both countries, most participants from both nations reported that they obtained information and decided to participate in clinical trials through the internet. In South Korea, although there were referrals from acquaintances, a significant number of participants registered directly with the Seoul National University Hospital Clinical Trial Center. In Japan, there is a system where participants are recruited through clinical trial recruitment sites operated by healthy volunteer recruitment companies and specific non-profit organizations, which then introduce them to medical institutions conducting the trials. Prospective participants find and apply for studies matching their criteria through these recruitment sites. Those who meet the criteria are referred to the medical institutions conducting the trials.

When asked if they experienced psychological stress in making the decision to participate, most Korean volunteers reported no significant stress, though they did express concerns about drug safety and side effects when participating in their first study. In contrast, Japanese applicants indicated that the conditions required for participation in clinical trials were a source of stress, highlighting a difference between the 2 countries.

In both countries, a significant number of respondents indicated that ‘financial reward’ was the primary motivation for participating in the study and the most important factor in making their decision to participate. Additionally, the majority of volunteers in both countries considered ‘financial reward’ to be a natural and expected motivation for participation. When evaluating the appropriateness of financial reward, respondents from both countries identified ‘time,’ ‘drug safety,’ and ‘use of the body in research’ as important factors.

Korean volunteers highlighted ‘drug components’ and ‘potential side effects’ related to ‘safety’ as crucial pieces of information about the clinical trial, while Japanese volunteers emphasized ‘financial information’ and ‘risks of side effects.’

When asked whether they informed others about their participation in the clinical trial, both Korean and Japanese participants indicated that they mentioned their involvement primarily to explain their absence. Notably, Korean participants sometimes chose not to inform their families to avoid causing unnecessary concern. In contrast, Japanese participants were more likely to inform their family members and relatives about their participation in the study. Additionally, one Korean participant mentioned that they describe their participation as going to “perform maruta” to explain their absence to acquaintances, despite not personally considering themselves as ‘maruta.’ They noted that this term helps others understand their involvement. Another Korean participant referred not to disclose their participation, citing the lack of awareness and negative views about clinical trials among people around them. This reflects the broader issue of negative perceptions stemming from insufficient information about clinical trials.

Regarding public perception of clinical trials, all Japanese participants believed that the public likely holds a negative view of clinical trials and participants. In contrast, some Korean participants were uncertain, responding with “I don’t know.” Nevertheless, participants from both countries agreed that the general public lacks knowledge about clinical trials, which leads to negative perceptions.

When asked who should participate in clinical trials, responses from both countries were similar, with answers such as ‘idle individuals,’ ‘those in need of money,’ and ‘people who view clinical trials positively.’ However, in Japan, one healthy volunteer suggested that clinical trials involving highly dangerous drugs should be conducted on ‘criminals’ or ‘death row inmates.’ This response suggests that healthy volunteers with experience in clinical trials might feel less ethical concern about exposing certain vulnerable groups to risk.

DISCUSSION

This study explored the sociodemographic characteristics, motivations, and factors affecting the enrollment decisions of approximately 120 healthy volunteers in Korea and approximately 130 in Japan. The study yielded several significant findings.

Overall, the responses from Korea and Japan were similar. The fact that Korea and Japan share the same cultural background could be one reason for this. Additionally, many respondents had prior experience with at least 2 clinical trials, which likely contributed to their familiarity with Phase 1 trials. A comparative analysis and summary of the responses from both countries have been provided.

In Korea, healthy volunteers were recruited by distributing questionnaires to individuals who had already participated in clinical trials, and data were collected afterward. In Japan, however, various methods were used to recruit healthy volunteers, and online platforms were already available at the time of the study. This suggests that access to research information was easier and the speed of recruitment was faster in Japan. Furthermore, since Japan managed a volunteer database, the higher proportion of first-time participants compared to repeat participants may reflect efforts to minimize exposure to risk.

When asked about discrepancies between their actual experience and what was reported, all respondents in Korea indicated no difference, while 7 respondents in Japan reported a discrepancy. This seems to suggest that the significantly higher level of satisfaction reported by healthy volunteers in Korea compared to those in Japan may have influenced the results. It might indirectly reflect a discrepancy between the information provided and the actual experiences of the participants.

Through the results of the questionnaire, 4 key themes related to healthy volunteers' participation in research were identified: financial reward, repeated research participation, safety, and negative perceptions. These themes provided insights into the perceptions and motivations of healthy volunteers. While some mentions of “health check-ups” or “curiosity” were made as motivations for participation, in reality, the majority of volunteers participated in the clinical trials primarily due to the “financial reward.” In the Japanese questionnaires, when asked, “Would you participate in the study if there were no financial reward?” all volunteers answered “no.” This indicates that their motivation is strongly centered on “financial reward.” Additionally, these volunteers believe that other respondents also participate in clinical trials primarily due to “financial reward.” Research has shown that healthy volunteers who participate repeatedly in studies are more likely to be motivated by financial reward compared to those with no prior study experience. Walsh and Nash conducted a survey of study participants and those without prior study experience. Their findings indicated that individuals with no previous study experience (52%) mentioned “financial reward” less frequently as a reason for participation compared to those with study experience (81%) [11]. In this survey, most respondents had participated in studies more than twice. It can be inferred that their repeated participation was likely motivated by “financial reward.” Thus, healthy volunteers who participate repeatedly are expected to be more motivated by financial incentives compared to others. The willingness to participate in research due to financial reward may dilute the voluntariness of healthy volunteers. True voluntariness of healthy volunteers can be regarded as making the decision to participate in research based on their own will, without being influenced by external circumstances or conditions. For healthy volunteers, financial reward can serve both as compensation for participation and as a means of recruitment. This phenomenon may be seen as conflicting with the principle of autonomy, one of the fundamental principles of bioethics.

Even though healthy volunteers often participate in research primarily due to “financial reward,” “safety” remains a critical factor in their decision to join a study. In clinical trials involving healthy volunteers, there can be an issue of disproportionate distribution between the risks and the benefits of participation. The risks and adverse effects of clinical trials are often unpredictable, and since healthy volunteers are primarily motivated by financial compensation, they may not deliberate sufficiently on these risks. Additionally, the reluctance to recommend participation to others is often due to concerns about the “risk of unpredictable adverse effects.” However, repeat participants tend to have greater trust in the safety of studies due to their prior positive experiences and may become less sensitive to safety concerns over time. In fact, respondents displayed a lack of familiarity with the details of the studies they had participated in. Respondents in the study believe that the general public holds a negative view of clinical trials. This perception often leads them to be hesitant about disclosing their participation to others or recommending participation. The belief that clinical trial participation should be limited to “idle individuals” or “those in financial need” reflects their own perceptions of healthy volunteers. Healthy volunteers participate voluntarily, yet they may still be exposed to greater risks than others. Although clinical research serves the special purposes of advancing science and public health, not only are healthy volunteers exposed to unforeseen risks, but they also do not directly benefit from the investigational drugs being tested in clinical trials. The participation of healthy volunteers in research should therefore be conducted with careful consideration of both the principle of non-maleficence and the principle of beneficence.

This study identified the characteristics of healthy volunteers in Korea and Japan. Its significance lies in being the first study to compare the characteristics and perceptions of healthy volunteers between the 2 countries. Although the survey was conducted at a single institution, the findings show that, despite being in the same Asian region, differences in perception may exist and that responses can vary depending on each country’s cultural background. Additionally, conducting comparative studies like this one regularly, every few years, would allow for tracking trends over time, leading to a deeper understanding of healthy volunteers participating in Phase 1 clinical trials in each country. In the short term, comparative studies including more Asian countries can be conducted, and in the long term, longitudinal studies tracking changes over time can be pursued.

Through this study, we gained a comprehensive understanding of the perceptions of healthy volunteers regarding clinical trials in South Korea and Japan. Healthy volunteers tend to be less negative about clinical trials than the general public, due to their interest in research participation and the education they receive prior to enrolling in a study. However, the general public tends to have negative views about clinical trials. In a survey conducted among the general public, only 33% of respondents expressed a positive willingness to participate in clinical trials. Instead, negative perceptions were identified, such as rejection of placebo (81.9%), concerns about side effects (70.3%), feeling like being a test mouse or “maruta” (68.7%), and a sense of inconvenience (67.8%) [10]. We found that healthy volunteers need to receive sufficient education about the clinical trial process and safety. Furthermore, it appears that public education programs are necessary to improve the general public’s negative perceptions of clinical trials. To change the public’s negative perceptions, educational campaigns targeting the general population are needed to explain how clinical trials are conducted and how they contribute to new drug development and public health. In particular, it is important to use online platforms to objectively present the actual process of clinical trials. In addition, the feedback of healthy volunteers who participated in research, along with the outcomes of clinical trials, should be communicated transparently to the public. When covered by the media, reporting on clinical trials should be balanced rather than focused solely on “risks.”

This study compares the perceptions and experiences of healthy volunteers in Japan and South Korea. However, the data is outdated and does not reflect the perceptions of healthy volunteers after the coronavirus disease 2019 (COVID-19) pandemic. A survey was conducted during the COVID-19 pandemic to investigate the motivations of clinical trial participants and the factors influencing their decision-making process. When asked about motivational factors, the majority of respondents answered that “contributing to science” was either very important (43%) or somewhat important (46.3%). This was closely followed by the desire to “help people in the Netherlands,” which was deemed very important by 35.8% and somewhat important by 46.6% of respondents. “Financial compensation” and “personal experience with the disease” were the 2 factors most often classified as only a little important (40.9% and 31.5%, respectively) and not important (14.1% and 58.4%, respectively) [14]. Thus, since changes in clinical trial participation motivations can be observed, further research on the perceptions and motivations of healthy volunteers is needed in the current contexts of Korea and Japan.

In addition, conducting a study on healthy volunteers participating in Phase 1 clinical trials today and comparing the results with this study could be valuable. Additionally, expanding the comparison beyond South Korea and Japan, which share a similar cultural background, to include healthy volunteers from Western countries would also be meaningful.

SUPPLEMENTARY MATERIAL

Supplementary Data 1

Survey questionnaire form