Introduction

Liver cancer is a common malignancy. A survey by the International Agency for Research on Cancer revealed there were approximately 906,000 new cases of liver cancer in 2020, accounting for 4.7% of all cancer incidences. Moreover, liver cancer led to about 830,000 deaths in 2020, accounting for 8.3% of all cancer-related deaths and the second highest mortality rate of cancer among men1. Considering the insidious onset of liver cancer, although early screening is possible with methods including liver ultrasonography, serum alpha-fetoprotein assay, and liver cancer risk assessment2, the proportion of patients who are suitable for radical surgery at the first diagnosis is still below 30%3. Systemic antitumor therapy is crucial for treating advanced liver cancer.

Background

A clinical drug trial is the systematic study of a drug in an individual (patient or volunteer) to determine drug safety and efficacy4. The success of these trials relies heavily on the number and characteristics of the recruited participants. However, motivating patients to participate in clinical trials is challenging. The low rate of active participation and compromised compliance due to passive participation highlight the importance of understanding patients’ attitudes toward clinical trials5,6. Previous research has suggested that patients’ participation in clinical trials is directly affected by their awareness of the trials.

Currently, cancer patients in China have limited awareness of clinical drug trials, with only 54.6% possessing a correct view7,8. Research is scarce regarding the specific aspects of patients’ insufficient awareness of clinical drug trials, their individual differences, and factors affecting participation. Studies have shown that the public awareness of clinical drug trials is significantly lower in China compared to other countries9. This lack of awareness and understanding can lead to hesitancy and mistrust, further reducing participation rates. Additionally, there are inadequate official recruitment platforms and promotions on clinical drug trials in China, leading to insufficient access to relevant knowledge.

In summary, there are significant gaps in the awareness and understanding of clinical drug trials among liver cancer patients in China. Enhancing patient education, improving informed consent processes, and addressing patients’ concerns about drug safety and efficacy are crucial steps to improve participation rates in clinical trials.

The study

Aims and objective

This study identified the attitude of clinical drug trials among these patients and explored factors affecting their participation in order to promote the development of clinical drug trials for this population.

Methods

Design

We adopted a phenomenological research method to investigate the attitudes of patients with liver cancer toward clinical drug trials.

Sampling and recruitment

Between March and August 2021, patients with primary liver cancer were recruited from the hepatobiliary surgery department of a tertiary grade A cancer hospital.The sample size was determined based on the principle of data saturation. The recruitment covered a wide range of areas across the whole province, ensuring a diverse sample that included both urban and rural residents. This approach aimed to minimize bias in cognitive levels and provide a comprehensive understanding of patients’ attitudes toward clinical drug trials. Purposeful sampling was used, and the sample size was determined based on the principle of data saturation10.The sample size was based on the fact that no new topics were presented after the patient’s interview information was repeated, and 19 liver cancer patients who participated in the clinical trial were finally included.

Inclusion and exclusion criteria

The study included patients who were: (1) diagnosed with primary liver cancer according to the “Guidelines for the Diagnosis and Treatment of Primary Liver Cancer (2022 Edition)” (Bureau of Medical Administration, National Health Commission of the People’s Republic of China. Guidelines for the diagnosis and treatment of primary liver cancer, 2022); (2) without cognitive or language impairment and were able to express their thoughts; and (3) willing to participate in the study and provided written informed consent. We excluded those with: (1) serious physical diseases or other malignant tumors; and (2) mental disorders.

Interview

A draft interview outline was first formulated after a literature review and group discussions; the outline was used to pre-interview three patients with liver cance6,7,8. The draft was then revised based on pre-interview findings and further discussed by the research team before finalization.Adjust the interview outline in a timely manner based on the results of the interview. The main content of the interview outline is shown in Table 1.

Table 1 Interview guide questions.
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Data collection

A semi-structured in-depth interview method was utilized. The primary research tools were the researchers who were professionally trained in qualitative research and qualified to conduct interviews. Before the interview, The researchers will inform the patient of the research purpose, process, methods and the basic content of the interview, promise that all information obtained will be kept confidential, and any problems during the interview can be freely withdrawn., All interviews were conducted at the agreed time after the patient’s informed consent in a quiet and comfortable separate room. The researcher asked the interviewee questions according to the interview outline. Each interviewee was interviewed once for 20–30 min. With the interviewee’s consent, the interview process was recorded and notes were taken. During the interview, the researcher closely monitored the interviewee’s non-verbal expressions, including facial expressions and body motions. Any ambiguous information during the interview was promptly clarified, and leading questions and hints were avoided.

Trustworthiness

To ensure the trustworthiness of our findings, we employed several strategies. For credibility, we used triangulation by collecting data from multiple sources, including in-depth interviews and field notes, and conducted member checking by sharing preliminary findings with participants to confirm accuracy. We maintained a detailed audit trail to document all research decisions and changes. To enhance transferability, we provided rich descriptions of the research context, participants, and findings, and included a diverse sample from both urban and rural areas. Dependability was ensured through a systematic research process, using a consistent interview guide and Colaizzi’s seven-step method for data analysis, with two researchers independently coding the data and resolving discrepancies through discussion. Confirmability was achieved by maintaining objectivity, keeping a reflexive journal to document biases and decisions, and providing a clear audit trail to allow others to verify the findings. These measures ensured that our study’s findings are credible, transferable, dependable, and confirmable.

Data analysis

This study adopted Colaizzi’s seven-step method for data analysis11. To ensure data authenticity and accuracy, recordings were transcribed within 24 h of each interview. By combining onsite interview notes with situational recall, Lead researchers Luwen and Lijuan will listen carefully and repeatedly to the recordings and analyzed the data word by word.Both Interviewer are senior nurses with more than 10 years of clinical nursing experience and have undergone systematic training.Once important statements were extracted, recurring and meaningful opinions were coded and divided into different categories to determine similarity. After a theme was sublimated, it was verified with the interviewee. The recordings were transcribed and organized by two researchers who independently extracted codes, categorized participants, and summarized themes. Upon disagreement, consensus was reached via group discussion to ensure result accuracy.

Ethical considerations

This study was performed in line with the principles of the Declaration of Helsinki. Ethical approval was granted by the Ethical Committee of Hunan Cancer Hospital (Ref. No: 2022-98).

Findings

Participants

Nineteen patients with primary liver cancer (A1–A19) were interviewed. Their general information is presented in Table 2. Most were male (84.2%), had a monthly income of < RMB 1500 (47.4%), had an educational level of junior high school (52.6%), and had rural cooperative (63.2%) and rural (57.9%) type medical insurance. The mean age of the participants was 56.47 ± 10.20 years. Most (52.6%) did not have previous experience in clinical trials.

Table 2 General participant information.
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Themes

Two major themes were yielded: differences in patients’ attitude of clinical drug trials and factors affecting participation in clinical drug trials. Illustrative quotes for each theme are presented in the text and in Table 3.

Table 3 Identified themes and example quotations.
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Theme 1: Differences in patients’ awareness of clinical drug trials

Insufficient attitude

Only nine participants had previously participated in clinical trials. Although those without previous experience in clinical drug trials had heard of such trials, they were unaware of relevant laws and regulations or their rights and obligations; even participants who had participated in clinical trials demonstrated insufficient understanding of these aspects. Since these participants urgently required relevant information on clinical drug trials, researchers explained it to them individually to allow them to fully understand clinical drug trials and, on this basis, actively engage in them.

Doubts and concerns

Nine participants expressed significant doubts and concerns about the safety, efficacy, and side effects of clinical trials. Further, two participants mentioned that the screening period was extensive, and that they were concerned that the waiting period when no treatment was provided could aggravate disease progression. A1: “The waiting period is too long, during which you receive no treatment for 10–20 days. I felt very anxious during the waiting period, and was wondering if some other medicine should be prescribed to control the disease to some degree.” A2: “We have waited for at least 21 days without taking drugs. I am already sick, and yet the trial does not let me take any medicine for many days.”

Blind trust

Once patients learn they have liver cancer and the disease has progressed to the middle or advanced stage, they rely more on professional doctors. Most patients place their hopes on authoritative hospitals or professors for new treatment methods. The inherent belief that clinical drug trials represent the latest and best drug treatment makes patients have high expectations.

Rational participation

Two participants stated that they proactively learned the basic information of clinical drug trials by consulting professional doctors, browsing the internet for relevant information, and asking other patients with previous experience. Since they had a good understanding of the pros and cons of clinical drug trials, they were able to approach the clinical trial rationally and actively participate in the treatment.

Theme 2: Factors affecting participation in clinical drug trials

Positive factors

Doctor’s recommendation

Most participants in this study mentioned that they participated in clinical drug trials owing to the recommendation of their attending physicians.

Expectations and hopes

In this study, most patients’ disease was in the middle or advanced stage, and surgery was infeasible. Since existing treatment methods could introduce serious side effects without producing satisfactory outcomes, participants had high expectations of clinical trial drugs.

Peer effect

For some patients with liver cancer, in addition to the influence of medical personnel, whether patients with the same disease had participated in clinical trials seemed to affect their willingness to participate in trials. Three participants stated that they participated in the trial because patients in the same village/ward participated and felt that the drug had good efficacy.

Economic burden

The high cost of liver cancer treatment has brought a huge economic burden to patients’ families. In this study, most participants were male. Under traditional Chinese Confucianism, it is generally believed that men are the economic backbone of the family. If they become ill, male patients receive no further economic income and still have to take the responsibility of caring for parents, raising children (minors), and paying medical, transportation, and other expenses. Therefore, the disease has significantly increased the economic burden on non-wealthy families. Thus, the fact that clinical drug trials are free and can reimburse some transportation costs can alleviate the economic burden on families. In this study, nine participants participated in clinical drug trials because of the family’s financial burden.

Contribution to the cause of medicine

Two participants mentioned that they could contribute to medical research by participating in clinical drug trials; this provided them with a sense of value even though they were ill.

Family support

Five participants stated that they were willing to participate in clinical drug trials because of the support or advice of their family. One participant refused to participate in a clinical trial despite family support. Contrastingly, one participant insisted on participating in a clinical drug trial (due to economic burden) despite the objection of his family. The other five participants (A9, A14, A16, A17, and A19) who had not participated in clinical drug trials claimed that their participation would depend on their thoughts, and they believed that family members’ opinions were only for reference.

Negative factors

Drug side effects

Five participants who had previous experience in clinical drug trials mentioned that the drug side effects were significant, and that they were concerned with the efficacy of the drug and whether their physical conditions could sustain the drug. Two participants withdrew from trials due to a deteriorating physical condition.

Drug safety

Four participants who had not participated in clinical drug trials expressed that their major concern regarding clinical drug trials was drug safety given that these drugs may have many unknown side effects. They mentioned being afraid of these drugs further impacting their health.

Incapability to ensure individual rights

Six participants in this study who had participated in clinical drug trials mentioned that the reimbursement period was too long, which led to doubts about reimbursements and lack of confidence in clinical coordinators. Some of them mentioned doubting whether the costs would ever be reimbursed.

Discussion

Differences in the attitude of clinical drug trials among patients with liver cancer

This study showed differences in attitude regarding clinical drug trials among liver cancer patients. Most patients had insufficient attitude concerning clinical drug trials and required relevant information, which is consistent with the findings of Huang, H et al. and Qi J et al. Numerous clinical trials on antitumor drugs have recently been conducted in China, greatly increasing the demand for participants12. However, the number of available participants is limited compared to the amount of newly diagnosed liver cancer patients. A study suggested that participant recruitment affected clinical trials13. Patients’ participation in clinical drug trials highly depends on their attitude of the trial revealed that a higher patient attitude of clinical drug trials increased active participation14. Therefore, it is crucial to raise public attitude of clinical drug trials.

Internationally, countries have introduced measures such as setting up popular science websites and holding scientific and educational activities for clinical drug trials15,16, which have successfully increased public awareness of clinical drug trials from 68–74%17. In contrast, the amount of domestic scientific education on clinical drug trials is extremely limited. Huang, F, et al. surveyed cancer patients’ attitude of clinical drug trials and reported that only 54.6% of the patients had a correct overview of clinical drug trials, whereas the attitude of relevant laws and regulations, medical expenses, and economic compensation was as low as 50%. Alternatively, Cao,.et al. conducted a survey on the attitude of clinical drug trials among outpatients at the departments of internal medicine, surgery, and obstetrics and gynecology in a hospital, and found that not only was the rate only 31.02%, more than half of the patients lacked a correct understanding of clinical drug trials18. Factors that have contributed to the differences in the attitude of clinical drug trials of patients in China are outlined below.

The first involves differences in cognitive methods. Most studies measure patient attitude of clinical drug trials by assessing whether they have “heard” of the trials. However, a study indicated that whilst the attitude rate of clinical drug trails was high, only few participants held a correct understanding of the trial19. This finding indicates that the nurses need to promote the clinical trial among liver cancer patients.

The second factor concerns insufficient publicity and education on clinical drug trials. Currently, there are inadequate official recruitment platforms and promotions on clinical drug trials in China. Therefore, the public has insufficient access to relevant knowledge on clinical drug trials and predominantly relies on recommendations by medical personnel, implying that the attitude of clinical drug trials among patients with liver cancer should be promoted via other methods. First, as nurses, who have the closest contact with the patients, we can improve the doctor-patient relationship and encourage patients to join the promotion of clinical drug trials. Relevant information should be delivered via simple and straightforward written and oral educational material to increase public attitude. Second, the internet should be utilized to establish additional popular science websites that can strengthen the delivery and education of basic knowledge on clinical drug trials, thereby reducing patients’ concerns.

The third factor is insufficient informed consent. Although patients with previous experience in clinical drug trials demonstrate a better attitude than those without such an experience, their attitude regarding aspects, including financial compensation, legal protection, and overview of clinical drug trials, is not necessarily superior[8]. This possibly highlights the reasons underlying insufficient informed consent and the weaknesses in the process of clinical drug trials. The finding implies that the primary investigators need to design a more rigorous and comprehensible informed consent form, and ensure the effectiveness and adequacy of informed consent. Nurses can facilitate the process of informed consent.

Factors affecting the participation of patients with liver cancer in clinical drug trials

The factors affecting the participation of patients with liver cancer in clinical drug trials in this study were consistent with those reported by Huang, Fan, et al. and Lang et al.20. The current study found that factors that would promote the participation of patients with liver cancer in clinical drug trials included a doctor’s recommendation, expectations, peer effect, economic burden, contribution to the cause of medicine, and family support, with a doctor’s recommendation being the most important, which is consistent with the results of relevant research. Jacobs et al. suggested that doctors were crucial in the process of participant recruitment during clinical trials21. Similarly, Lang et al. indicated that a doctor’s recommendation was the key reason for cancer patients consenting to clinical drug trials20. Therefore, to improve patients’ participation in clinical trials, it is crucial to fully utilize doctors.

Another factor that encouraged patients in this study to participate in clinical trials was the economic factor. Since most patients enroll in clinical trials to gain access to free treatment, transportation subsidies, and other benefits, it is established that medical benefits are a critical motivation for patient participation. Family support also plays an important role in encouraging patients to participate in clinical drug trials. Under the subtle influence of traditional Chinese Confucianism, individuals are closely bonded with their family. Therefore, whether a patient should participate in a trial is not a personal decision but rather a family decision. However, some researchers do not fully understand this complexity regarding patient participation in clinical drug trials. Moreover, most researchers notify patients without assessing if the information is relevant to the patient, whereas family members usually understand the real needs of patients when making decisions. Therefore, researchers should pay attention to the important role of family support in patients’ participation in clinical drug trials.

Other factors that motivated patients in this study to participate in clinical drug trials included expectations, peer effect, and contribution to the cause of medicine. Our findings showed that: (1) some patients placed their hopes on new drugs/treatment methods, expecting them to provide better medical experience and treatment outcomes; (2) a small number of patients gained confidence regarding treatments from the successful experience of others; and (3) two patients withdrew because of side effects. The patients hoped that the medical research field in China would develop rapidly, and new drugs for the treatment of liver cancer would be invented to alleviate patients’ pain. At the same time, they understood that the clinical application of new drugs relied on clinical trials, and therefore decided to contribute to medical research by participating in clinical trials.

Factors that discouraged patients from participating in clinical trials mainly included drug side effects, drug safety, and the incapability to ensure individual rights. Drug efficacy, side effects, and safety were the participants’ greatest concerns. Therefore, before trials, researchers should fully inform the patients of the risks, grouping methods, and possible adverse reactions, as well as establish emergency plans. During a trial, adverse reactions should be closely monitored and treated, and a standardized management process should be implemented. Financial compensation is also pivotal in clinical drug trials. In this study, six participants mentioned that after participating in clinical trials, the promised reimbursements were not paid promptly, thereby causing their mistrust of the clinical coordinators. Presently, there are multiple pharmaceutical companies in China, each with different reimbursement systems. Reasonable economic compensation for clinical trial participants is both an ethical and legal requirement. Therefore, corresponding regulations should be improved, and the reimbursement process and period should be optimized to protect the interests of trial participants. Nurses can provide emotional support to relieve the participants’ distress related to the financial issues.

Strengths and limitations of the work

This study used qualitative interviews to explore the attitude of patients with liver cancers toward clinical drug trials. However, this study had certain limitations. First, although we tried to include participants with the maximum amount of variation in characteristics, the youngest participant was aged 39 years. In future studies, it may be beneficial to include young patients to capture their views on clinical trials. Second, the results may be limited in terms of generalizability as all the participants were recruited from a single hospital. The patients’ perceptions of participating in clinical trials may vary with their experience at different hospitals.

Conclusion

This study investigated the attitudes of patients with liver cancer toward clinical drug trials by performing qualitative interviews with 19 patients with primary liver cancer. Two themes were highlighted from the interviews. Our results can help medical staff gain an in-depth understanding of the attitude of clinical drug trials among patients with liver cancer and their individual differences as well as factors affecting their participation. Nurses can improve the attitude of clinical drug trials among patients with liver cancer and, based on this, encourage participation by specifically targeting the provision of relevant information on clinical drug trials.