Ethical challenges of placebo use in herbal medicine trials: multiple stakeholder perspectives from qualitative interviews

Abstract

Background

The ethical use of placebos in herbal medicine (HM) clinical trials remains contested, particularly in contexts where traditional medical systems shape patients’ beliefs and expectations. Complexities in placebo preparation, insufficient transparency, and inconsistent consent practices pose challenges not only to scientific validity but also to ethical standards. This study aimed to explore stakeholder perspectives on placebo use in HM trials, with a specific focus on ethical concerns related to trust, informed consent, and trial integrity.

Methods

In-depth qualitative interviews were conducted with 23 stakeholders, including clinical investigators, research coordinators, trial managers, pharmaceutical staff, and patient representatives. We applied an inductive, framework-based thematic analysis to identify key perceptions, challenges, and needs regarding placebo use.

Results

Participants demonstrated diverse understandings and attitudes toward placebos. Medical professionals, who often had higher levels of formal medical training, tended to describe placebos from a scientific perspective, whereas patients more commonly expressed skepticism rooted in concerns about trust and transparency. Pharmacists reported substantial challenges in developing indistinguishable HM placebos, raising questions about the ethical implications of adding small amounts of active ingredients. Participants also highlighted inconsistent practices in placebo composition and similarity evaluation, which raised concerns about blinding integrity and transparency, as well as insufficient communication that affected participant trust and overall trial integrity.

Conclusions

Differences in professional and educational background appeared to shape how stakeholders perceived HM placebos, influencing informed consent and ethical conduct in trials. Enhancing understanding and transparency in placebo composition and similarity evaluation is essential to uphold ethical and scientific integrity of HM trials and to guide the development of clear guidelines for HM placebo design and communication.

Clinical trial number

not applicable.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12910-026-01412-8.

Background

In recent years, the number of herbal randomized controlled trials (RCTs) has grown significantly, driven by the widespread use of herbal medicine (HM) across diverse populations [1–3]. While RCTs are considered the gold standard for evaluating treatment efficacy, the use of placebos in HM trials presents unique challenges, not only from a scientific perspective but also from ethical, social, and cultural standpoints. The inherent characteristics of HMs, such as their complex composition, distinctive odors, and natural origins, make the development of indistinguishable placebos particularly challenging [4, 5], thereby complicating the design and execution of rigorous placebo-controlled trials.

Conducting HM trials involving placebos requires the engagement of multiple stakeholders bringing differing perspectives, roles, and expectations. Patients’ willingness to participate may be influenced by limited understanding or mistrust of placebo use [6, 7], while healthcare providers’ everyday experiences with placebo-like interventions, which is clinical practices or features of the therapeutic context, such as communication, expectations, and the care setting, that elicit placebo or nocebo effects without administering an inert substance, may shape their communication practices and ethical judgments [8–10]. These divergent viewpoints can impact trial integrity, transparency, and participant autonomy.

As ethical standards for clinical trials evolve globally [11], there is increasing scrutiny of how placebos are produced, described, and explained to participants, especially in culturally specific contexts like HM. Issues such as the inclusion of active ingredients in placebos in order to improve sensory similarity and insufficient disclosure of placebo composition raise significant ethical concerns. Adding pharmacologically active substances to mimic herbal characteristics may compromise the inert nature of placebo, introducing potential physiological effects and blurring the distinction between intervention and control. The exclusion of participants from placebo evaluation processes raises important ethical questions about informed consent, deception, and respect for persons.

Given these challenges, this study aims to explore the ethical and experiential dimensions of placebo use in HM clinical trials by analyzing the perspectives of key stakeholders. Through in-depth qualitative interviews, we seek to identify areas where ethical standards may be compromised and offer insights for enhancing the transparency, accountability, and ethical robustness of future HM research.

Methods

Study Design

This qualitative study was designed to investigate the perspectives of multiple stakeholders involved in HM clinical trials regarding the quality and application of HM placebos. A qualitative approach was chosen for its strength in exploring complex phenomena within their specific contexts and allowing for the emergence of in-depth insights from participants’ experiences and perceptions. Semi-structured interviews were conducted to facilitate a flexible yet focused dialogue around the central themes of the study [12]. This study was approved by the Ethics Committee of Dongzhimen Hospital, Beijing University of Chinese Medicine. (Approval Number: 2022DZMEC-352-02). All participants provided informed consent prior to participation in the interviews, ensuring confidentiality and voluntary involvement.

Participant Recruitment

Participants were purposively selected to ensure a rich variety of perspectives on HM placebos. The recruitment strategy aimed to include a broad spectrum of roles in HM clinical trials, including clinical doctors, research nurses, patients, pharmaceutical personnel, Clinical Research Coordinator (CRC), Clinical Research Associate (CRA) and students. Potential participants were identified through HM research networks and professional organizations, as well as through referrals from initial interviewees. Inclusion criteria required participants to (1) have direct or indirect experience with herbal medicine clinical trials within the past five years, (2) be able to provide informed consent, and (3) possess sufficient communication skills to participate in a qualitative interview.

Recruitment was not conducted separately for each group but aimed to ensure adequate representation and data saturation across stakeholder categories. The selection of sample size in this study follows two principles. First, interview data saturation was considered achieved when no new themes emerged from the same stakeholder category on a given issue [13]. Second, the interview data were sufficient to answer or explore the research questions and objectives, meaning that the collected data could explain participants’ attitudes and perceptions and the underlying decision-making processes [14, 15]. Although the concept of data saturation is frequently used to justify sample adequacy in qualitative research, we acknowledge ongoing debates regarding its conceptual usefulness [16]. In this study, we use saturation pragmatically to indicate that the dataset provided sufficient richness and relevance to address the study aims, rather than implying complete informational closure.

Data collection

Interview Guide

The interview guide was developed based on an extensive literature review [4, 17–21] and expert consultations. The final themes and corresponding questions included in the interview are presented in Table s1 (Supplementary file 1). The interview guide included questions on understanding of the placebo; participation in clinical trials involving placebos; production process of HM placebos; evaluation of HM placebos.

Interview procedures and content

The interviews were conducted between the 10 February 2023 and 8 March 2024. These semi-structured interviews were conducted by face-to-face communication at the participant’s workplace and online meeting. Online interviews were conducted via WeChat, a widely used and secure communication platform in China that provides stable audio/video connections and supports confidential one-on-one interviewing. The interviewer was guided by open ended questions structured around the participants’ experiences, which allowed for the exploration of predetermined topics while providing the flexibility to pursue emergent themes.

We informed the interviewees that all information would be handled confidentially and published in an anonymous format. The interviewees consented to audio recording, which were first transcribed using automatic speech-recognition software and then manually reviewed and corrected by two authors (XZ and JG) to ensure verbatim accuracy.

Research team and reflexivity

The research team consisted of members with backgrounds in herbal medicine, qualitative research, medical ethics and clinical epidemiology. All team members share an academic interest in the ethical dimensions of herbal medicine research but hold no financial or institutional conflicts of interest related to the topic. The interviewer (XZ) is a postgraduate researcher trained in qualitative methods, who maintained reflexive notes after each interview to record assumptions and potential influences on data interpretation (Supplementary file 2), aligning with Consolidated Criteria for Reporting Qualitative Research (COREQ) guidelines (Supplementary file 3) [22]. Team discussions were held to cross-check interpretations and enhance reflexivity throughout the analytic process. XZ briefly introduced himself to the interviewee and did not disclose any more personal background information unless asked. The study was supervised by Professor CZ, who provided guidance to ensure the rigorous conduct of the interview. There was no contact between the investigators and the participants before the start of the study.

The team recognized that the cultural and institutional context of HM in China, where herbal treatments are widely integrated into mainstream healthcare and carry strong cultural legitimacy, could shape stakeholders’ perceptions of placebo use and ethical acceptability. Acknowledging this context allowed the team to interpret the findings within the local setting and to reflect on their transferability to other cultural and regulatory environments.

Data analysis

Interview quotations originally in Chinese were translated into English for analysis and presentation. The primary translator was a bilingual researcher (YL) with academic training in both Chinese medicine and qualitative research. All translations were cross-checked by another bilingual team member (CZ who is highly proficient in academic English and has published multiple peer-reviewed English-language articles.) to ensure linguistic accuracy and preservation of meaning. When necessary, subtle cultural terms related to herbal medicine were discussed within the team to reach consensus on the most appropriate English expressions. Key quotations were additionally reviewed by a native English speaker to confirm clarity and fidelity to the original meaning.

This study utilized thematic framework analysis, an inductive and matrix-based approach, for organizing and analyzing qualitative data. The analysis consisted of three main steps: [23]

Data Familiarization

All interviews were initially transcribed by speech-recognition software and subsequently checked and corrected by the researchers to ensure verbatim accuracy. Researchers repeatedly listened to the recordings and annotated potential themes and subthemes. The data was systematically organized according to interview outlines and categorized by location or interviewer identity as needed. To ensure consistency and minimize bias, a single researcher (XZ) conducted all interviews. All participants reviewed the content of their interview transcripts during the verification process, and one participant further requested a specific check to confirm that all identifiable details had been fully anonymized. Verbatim transcription, team cross-checking, and reflexive documentation were used to ensure data integrity.

Data Coding

The coding process began with open coding using NVivo software (Version 12 Plus, QSR International Pty Ltd., Melbourne, Australia), where initial themes were identified directly from the data. These themes were iteratively refined and grouped into broader themes, revealing patterns and relationships. One coder (XZ) conducted the initial rounds of analysis by analyzing the interview transcripts and developed initial codebooks for individual interviews. Other coders (YL, JG) using the refined codebooks, coded 25% of the transcripts and cross compared with the first coder. The core team (XZ, BQ, YL, CZ) met periodically to share perspectives and to develop consensus on the codes and underlying themes.

Text Classification

After coding, data segments reflecting similar thematic patterns were grouped and refined into overarching themes (Supplementary file 4). Themes were developed inductively across the whole dataset. Once the thematic structure was established, we undertook a post-hoc interpretive review to examine how participants in different stakeholder roles expressed these themes. This step allowed us to describe role-related variations as contextual insights rather than formal group comparisons. Researchers preserved the authenticity of participants’ narratives, retaining ambiguous data pertinent to the research objectives for further analysis.

Results

We conducted interviews with 23 participants, one of which was conducted via an online meeting. The participants came from diverse backgrounds with varying levels of education, ranging from high school to PhD programs, and had between 2 and 17 years of professional experience. The group included 17 females and 6 males [Table 1]. Among the 23 interviews, 12 lasted less than 20 min and the remaining were under 30 min, excluding time spent on consent, briefing, and debriefing. Most participants were experienced professionals familiar with clinical research processes and ethical discussions. The semi-structured guide was intentionally designed to focus on a narrow set of core topics, thereby avoiding lengthy biographical background or unrelated detail. Interviewers received specific training and used targeted follow-up probes to ensure that each core question was explored in sufficient depth. As a result, the interviews tended to be concise but information rich. We also analyzed the respondents’ attitudes towards seven related questions when applying the HM placebo [Figure 1].

Table 1.

Characteristics of Interview Participants

Characteristics	No. of interviewees (%)
Role
Doctor	5 (21.7%)
Nurse	2 (8.7%)
Patient	4 (17.4%)
CRA	5 (21.7%)
CRC	2 (8.7%)
Medical student	2 (8.7%)
Pharmaceutical personnel	2 (8.7%)
Nursing Aide	1 (4.3%)
Sex
Men	6 (26.1%)
Women	17 (73.9%)
Age
20–30	9 (39.1%)
31–40	5 (21.7%)
41–50	8 (34.8%)
51–60	0 (0.0%)
61–70	1 (4.3%)
Educational background
High School Diploma	1 (4.3%)
Bachelor’s Degree	14 (60.9%)
Master’s Degree	3 (13.0%)
Doctoral Degree	1 (4.3%)
NA	4 (17.4%)
Interview duration
0–20 min	12 (43.5%)
21–30 min	11 (47.8%)

CRA, Clinical Research Associate; CRC, Clinical Research Coordinator. For some interviewees who preferred not to disclose their basic information, "NA" is used to fill in the blanks

Fig. 1.

Stakeholders’ responses to key questions regarding the use of HM placebos. Bars represent the number of participants expressing positive (yellow), neutral (orange), or negative (blue) attitudes toward each question. Participants were asked: (1) whether they had participated in the quality assessment of HM placebos; (2) whether HM placebos should undergo safety evaluation; (3) whether they should match the active intervention in appearance; (4) whether it is acceptable for HM placebos to contain 5–10% of the original herb; (5) whether producing HM placebos is more difficult than chemical-drug placebos; (6) whether they would be willing to participate in HM placebo-controlled trials; and (7) whether they understood the definition of a placebo. a A total of 16 respondents provided interview information for this question. b A total of 14 respondents provided interview information for this question. c A total of 14 respondents provided interview information for this question. d A total of 14 respondents provided interview information for this question

The analysis revealed four overarching themes that together reflected stakeholders’ multifaceted views on HM placebos, encompassing their perceptions of the placebo concept, experiences and attitudes toward placebo-controlled trials, opinions on the production process of HM placebos, and views on placebo evaluation and quality assessment.

Understanding of placebo across different roles

The interviews revealed a spectrum of understandings about placebos among different stakeholders, reflecting variations in professional roles, educational backgrounds, and cultural perspectives.

Professional and scientific perspectives

Medical professionals, such as doctors and medical students, often viewed placebos through a scientific lens, describing them as “inert substances” used to differentiate treatment effects. However, the role of placebos in their daily practice also appeared to relate to broader social expectations to provide “something” to patients. As one doctor explained, she would sometimes offer vitamin C tablets to reassure anxious patients, illustrating the perceived social expectation of providing tangible treatment. She mentioned:

“You know, I think of placebos as something we use when we’re not really sure about the benefits or risks compared to actual medication. But the key thing is, it shouldn’t harm the patient. We use it to check out how well a real medication works by comparing two groups. Honestly, we use it quite a bit in practice, especially with those anxious patients who just can’t get a good night’s sleep, even after taking sedatives. Sometimes, I’ll just hand them a B6 or maybe even a vitamin C tablet and say, ‘Here, take this extra sleeping pill,’ and that’s usually enough to do the trick.”

Pharmaceutical personnel, in particular, are involved in the placebo preparation process based on a correct understanding of placebo.

……It’s supposed to have no pharmacological activity.

……now I know it has no pharmacological activity.

Pragmatic and socially driven understandings

In contrast, nurses and non-medical staff demonstrated limited formal knowledge about placebos, which may suggest a gap in clinical education and training. Given their crucial role in trial implementation, this limited understanding highlights potential challenges in communicating with patients and maintaining trial integrity.

CRC, CRA, and pharmaceutical personnel generally possessed basic knowledge of placebos, which appeared related to their practical experience and frequent participation in clinical trials. A CRA and CRC respectively mentioned:

“From where we stand in running clinical trials, a placebo is basically just something that doesn’t have any active ingredients.”

“I used to think of a placebo as just a blank control, maybe made of starch or something, and without any side effects.”

However, for staff not directly involved in clinical tasks, their understanding of placebos remains largely unknown. They mentioned:

I’ve heard or learned this term, but I might not have delved deeply into what a placebo is mainly used for.

I kind of remember hearing that taking a placebo can mess with your mind a bit, making you feel like it’s actually working.

Notably, our interviews found that a proportion of CRAs referred to the concept of placebo effects, recognizing that these effects may stem from psychological or emotional responses. CRAs mentioned:

“I kind of remember hearing that taking a placebo can mess with your mind a bit, making you feel like it’s actually working, even if it’s just a sugar pill.”

“I’ve realized that some illnesses can be influenced by this placebo effect, so it makes sense to include a placebo group in clinical trials. Some diseases seem to get better depending on how the patient feels mentally and emotionally.”

Patients’ lived experiences and lay interpretations

Patients, on the other hand, exhibited diverse understandings that appeared to be shaped by their social experiences and previous interactions with the healthcare system. One patient’s description of feeling like a “laboratory rat” when participating in a trial reflects broader societal concerns about trust, autonomy, and informed consent in medical research, patients said:

“ My dad was part of a clinical study for esophageal cancer, but honestly, I still don’t really get what it was all about.“

Never understood it.

Unfamiliar, no one in my family has medical knowledge.

These accounts illustrate that stakeholders’ understandings of placebo extend beyond its biomedical definition. Professional experience, clinical responsibility, and cultural beliefs together shaped how participants interpreted the legitimacy and moral acceptability of placebo use in practice. The specific content of the interview can be found in supplementary file1 table s2.

Attitudes and considerations of HM placebo

Professional endorsement of placebo-controlled trials

The medical professionals (doctors, nurses, and students) were all positive about participating in clinical trials using placebo and expressed a willingness to participate, viewing them as essential for scientific validation.

“Support placebo-controlled trials.”

Support, would consider participating.

“I’ll follow the doctor’s and the research protocol’s guidance, as long as it meets the requirements.”

“Support, would actively participate in placebo-controlled trials if needed.”

Reluctance and perceived risks of random assignment

While many clinical trial managers and pharmaceutical personnel were open to participating in placebo-controlled trials, they showed reluctance to be in the placebo group, especially when dealing with serious illnesses. A CRA noted:

" I’d definitely join in, especially if it’s for something serious, but I really don’t want to end up in the placebo group.”

However, patients showed mixed attitudes towards participating in clinical trials, with a general reluctance to be randomly assigned to the placebo group. Some patients described feeling like “laboratory rats” when participating in clinical trials, reflecting insufficient understanding of placebos and limited communication with physicians. Patients and CRC said:

“Depends on the condition, unless there’s no other medication available, generally, don’t want to participate.”

If someone doesn’t have patience, a lot of patients might drop out, saying they feel like they’re just being used as lab rats, especially if it’s a placebo….

As one patient expressed, “If participating, I don’t want to be in the placebo group… there’s still a risk, right? And yeah, that kind of worries me.” Another patient noted a more conditional openness, saying, “If the risks are low, yeah, I’d join in. After all, traditional herbal medicine is less harmful than Western medicine.”

Trust, communication, and informed consent

Trust in the doctor appeared to play an important role in shaping patients’ willingness to participate in clinical trials. Doctors noted that clear and empathetic communication is important for gaining patient cooperation in clinical trials. Doctors suggested that empathetic explanations could foster greater patient cooperation by helping patients understand potential benefits and risks. Limited communication between doctors and patients was perceived as a possible reason for patient withdrawal, highlighting the need to strengthen the informed consent process to support continued participation. For example, a doctor said:

“More people are down to participate, mostly because doctors actually take the time to talk to them, show they care, and break things down for them… But then you’ve got others who don’t do as well, maybe because sometimes doctors miss the mark, and then the patient just bails.”

A nurse also highlighted the importance of empathy during patient communication:

We try to comfort them, explain the treatment measures, and after a while they often feel calmer and more cooperative.

The study also found that the informed consent process usually does not provide a complete explanation of the placebo composition. Such ambiguity was viewed as potentially confusing or distressing for patients. A medical student said:

" When I was in the outpatient department, I saw this grad student recruiting patients with headaches, but they didn’t tell them they might end up in the placebo group, which feels like a pretty big ethics and rights issue to me.”

Participants’ attitudes toward participation revealed that decisions were not purely scientific or utilitarian but closely tied to trust and communication within the doctor–patient relationship. For many, willingness to participate reflected both confidence in medical professionals and concerns about fairness and informed consent. The specific content of the interview can be found in supplementary file1 table s3.

Challenges of preparing HM Placebos

Practical challenges in achieving sensory similarity

Simulating HM placebos presents unique challenges, with many clinical trial personnel agreeing that it’s considerably more difficult compared to chemical drugs. These challenges stem from the need to mimic the characteristic taste, smell, texture, and overall mouthfeel of HM without using active pharmacological ingredients. The complexity of these factors makes it hard to create placebos that resemble actual HMs. Doctors and clinical trial personnel noted that patients familiar with traditional herbal treatments can often detect differences in placebos. If a placebo lacks a specific taste, patients could suspect something is off, as many HMs have a distinct flavor profile.

If a patient has taken traditional medicine before, they should be able to feel the difference.

“Yeah, some placebos don’t have that medicinal taste. Like with capsules, you might catch a whiff of the medicine when you open it, but with placebos, you probably won’t.”

As one coordinator observed, “The smell is kind of similar, but when patients talk to each other, they start guessing who’s in the control group.”

Pharmaceutical personnel shared their experience in developing a placebo, noting that they encountered various issues with taste and consistency during the production process. The complexities of stabilizing the outer layer of the placebo and ensuring it doesn’t become too hard or crispy. They also mentioned the risk of aromatic substances molding at high temperatures, underscoring the delicate balance required in the production process.

……We ran into a lot of issues during the process, but in the end, we managed to produce a pretty good placebo.

“It’s not just about making it hard or crispy; the outer layer’s got to be stable but with a bit of roughness to it. Then, when you pop it back in the incubator, you can’t crank up the heat too much. With aromatic stuff, if you go over 60 degrees, it’ll start molding…”.

Ethical reflections on including active ingredients

Due to the special odor of HM placebo, many previous studies have added test drugs in the range of 5%-10% to imitate the physical properties of the test drugs. However, in this interview doctors, medical students, and clinical research personnel expressed that any amount of the original drug could interfere with the placebo’s non-pharmacological nature, complicating the trial’s outcomes. They do not understand whether it is reasonable to add 5% to 10% of drugs to HM placebos to simulate appearance and taste.

I don’t support it; that’s a matter of low dosage, which doesn’t really count as purely placebo.

“ I’m kind of on the fence; it’s hard to say, you know? If your drug’s doing something, and then you add something else, it’s tough to figure out. The placebo might have its own effect, right? And then throwing the drug into the mix makes it even harder to tell what’s going on.”

I’m neutral on it—not really all for adding the original drug. But with how tough it is to mimic traditional herbal medicine placebos, it’s kind of a tricky situation….

Several participants distinguished between what they described as a “true” or “pure” placebo, completely inactive, and those containing small amounts of active ingredients to enhance similarity. Most regarded only the former as a scientifically and ethically legitimate control, expressing concern that an “impure” placebo could distort results or violate the spirit of randomization. These accounts highlight a recurring dilemma between scientific fidelity and ethical purity, while adding minimal active ingredients improves sensory similarity, it also blurs the moral boundary of what constitutes a ‘true’ placebo. Such ambivalence exposes the practical–ethical tension underlying HM placebo production. The specific content of the interview can be found in supplementary file1 table s4.

Evaluation of HM placebo

Limited involvement and awareness of placebo evaluation

All surveyed participants were not involved in the placebo similarity evaluation. In HM trials, similarity evaluation refers to assessing how closely a placebo matches the active formulation in appearance, smell, and taste. This process is part of the broader placebo evaluation framework, which also includes safety and applicability assessments typically conducted by specialized technical institutions.

Don’t know about the placebo evaluation you’re talking about.

Don’t know, haven’t been involved in what you call placebo evaluation.

Haven’t participated in the scoring evaluation you mentioned…….

This limited awareness suggests that evaluation procedures are often confined to specific technical teams, leaving most clinicians and coordinators unfamiliar with how placebo quality is assessed.

Similarity as the core criterion for scientific credibility

The interviews revealed that the two most focused characteristics of a placebo are its similarity to the test drug and its safety. In clinical trials involving herbal medicines, the similarity between the placebo and the actual drug is crucial to prevent unblinding. However, during the blinding process, doctors often pay little attention to the subtle differences between these drugs.

I can’t tell the difference between the drugs when I’m here—they’re all just big white boxes. I have no clue which one’s real and which one’s not, and there’s no way to tell just by looking at them.

These accounts suggest that while similarity ensures methodological rigor, the evaluation of placebo appearance and sensory features is rarely formalized or systematically monitored.

Safety and transparency as ethical dimensions of evaluation

Additionally, the emphasis on safety reflected broader societal expectations for transparency and ethical conduct in clinical trials, suggesting that future HM trials should prioritize clearer communication about placebo composition and potential risks. One CRA mentioned:

“……We confirm the excipients and clearly inform in the protocol, including informed consent, because some ingredients might not be suitable for specific groups.”

A medical student similarly noted, “I haven’t participated in placebo evaluation, but I think safety is a bit more important—though from a researcher’s view, similarity also matters.”

When discussing the evaluation of HM placebos, participants emphasized transparency, safety, and credibility as key indicators of quality. Their reflections suggest that ethical evaluation was understood not as a checklist but as an evolving process of balancing methodological rigor with moral responsibility. The specific content of the interview can be found in supplementary file1 table s5.

Discussion

Understanding and transparency in placebo use for HM trials

The observed variance in placebo understanding among participants, especially patients and some non-professionals, is not merely an educational or communication gap; it reveals a deeper ethical vulnerability within HM clinical trials. The hesitation, distrust and reluctance toward placebo allocation expressed by participants directly engage several key ethical principles.

First, these findings pose a significant challenge to the effectiveness of the informed consent framework. Ethical informed consent is not just the act of signing a form but an autonomous authorization based on a genuine understanding of the study’s nature, risks, and alternatives. Our results suggest that due to informational asymmetry, which is further exacerbated in the specific cultural context of HM by traditional beliefs and inherent expectations of herbal efficacy, many participants may not achieve procedural comprehension. Instead, they may rely on relational trust in their physician or the medical system as a substitute for a detailed understanding of the research. This “trust” substitution, while common in clinical practice, is ethically precarious in research, as it can lead to consent being given without full information, thereby compromising participant autonomy.

Second, this relates directly to the core ethical cornerstone of trust in clinical research [11]. The centrality of trust in the patient-physician and researcher-participant relationship, a key finding in other qualitative studies on placebo acceptability [24], means that this fragile, relational trust is easily eroded when participants feel confused or perceive that information is being withheld, such as opacity regarding placebo composition. This loss of trust not only leads to individual trial withdrawals but also damages public confidence in the entire field of HM clinical research.

Finally, our findings reveal potential issues of injustice in explanation and procedural justice. In the specific cultural context of HM trials, structural asymmetries in information, like the discrepancy between the scientific paradigm of the researchers and the participant’s understanding framework based on traditional medicine, can create an inequity, namely that participants who are informationally disadvantaged bear a greater burden of comprehension during the consent process. If the communication strategies fail to acknowledge and bridge this comprehension gap, the consent process itself is procedurally unjust. Ensuring justice is not only about participant selection but also about their access to a fair, transparent, and understandable explanation.

To address these challenges, targeted educational initiatives are needed to enhance both public and professional understanding of placebo use while reinforcing informed consent and transparency [25]. Educational programs focused on the placebo effect could be instrumental in dispelling misconceptions and alleviating fears [26, 27]. For these programs to be effective, they must be accessible, culturally sensitive, and tailored to audiences from diverse backgrounds using multimedia and interactive formats [28, 29]. In parallel, healthcare professionals and trial personnel should receive ethics-oriented training in placebo mechanisms, risk communication, and participant rights, enabling them to fulfill their ethical obligations during recruitment and consent processes.

Beyond education, building trust with participants requires structural transparency. Providing information alone is insufficient; participants must understand how their contributions advance medical knowledge [30]. Tailored, personalized discussions that consider individual backgrounds and comprehension levels can demystify the purpose of placebos, framing them as scientific tools rather than deceptive measures [31]. The current lack of transparency in the preparation and evaluation of HM placebos raises critical ethical concerns. Many clinical trials do not disclose placebo compositions, compromising informed consent and potentially eroding participant trust. Transparent communication about placebo preparation procedures, including safety protocols and quality controls, is essential for participants to appreciate both the risks and social value of trial participation. Openly acknowledging each participant’s contribution, whether receiving an active treatment or placebo, can improve cooperation and reinforce the ethical standards that underpin clinical research.

This emphasis on transparency and participant respect is consistent with recent international ethical guidance. The Declaration of Helsinki clarifies that placebo controls should only be used when scientifically justified and when participants are not exposed to serious or irreversible harm. This principle resonates with participants’ concerns about the use of placebos in serious conditions and underscores the need to balance scientific rigor with the duty of care in HM clinical research.

Challenges in HM placebo preparation and evaluation

Developing placebos that accurately mimic the sensory properties of herbal medicines is essential to maintain blinding integrity but presents unique challenges. HM placebos must replicate the taste, smell, and appearance of active treatments without containing pharmacologically active components [32, 33]. Some studies have addressed this challenge by adding small amounts of the original herbal drug to improve sensory similarity; however, such addition introduces potential pharmacological effects, compromising the non-pharmacological nature of placebos and the integrity of trial outcomes. In contrast, the use of inert excipients or flavoring agents without therapeutic activity is considered acceptable and does not affect placebo validity. Innovative approaches, including advanced technologies like electronic noses and tongues, offer potential solutions for creating placebos that closely resemble HMs in sensory aspects while maintaining pharmacological neutrality [34–36]. Collaboration across disciplines, including pharmacology, chemistry, and technology, can further drive innovation and improve placebo quality.

Our study also identified a notable lack of trial personnel involvement in the evaluation of HM placebos, pointing to deeper concerns about procedural transparency and ethical oversight. When those directly administering the interventions are excluded from placebo assessment processes, opportunities for detecting quality issues, sensory inconsistencies, or participant feedback are missed, potentially compromising both trial integrity and ethical accountability. Safety remains a critical ethical concern, particularly given the complex and sometimes opaque composition of HM placebos, which may carry unexpected risks if not rigorously evaluated [37]. Comprehensive testing and routine safety monitoring should not only be viewed as scientific necessities but also as ethical obligations to protect participant welfare. The integration of advanced technologies, such as electronic sensory evaluation tools and machine learning algorithms, holds promise for improving the accuracy and reproducibility of placebo design [38–40]. However, technical innovation alone is insufficient. The preparation and evaluation of HM placebos must be governed by internationally recognized ethical and methodological frameworks that explicitly balance scientific rigor with participant rights and expectations. In addition to existing Good Clinical Practice (GCP), more specific guidance is needed to ensure transparent and reproducible placebo design. The TIDieR-Placebo framework [41], for instance, offers a structured approach for reporting key features such as placebo composition, sensory similarity, and manufacturing rationale. Integrating such frameworks into HM trial protocols and registries could promote consistency in design, facilitate ethical review, and enhance cross-cultural comparability. Furthermore, journals and regulatory agencies should explicitly require detailed placebo reporting as part of publication and registration standards. Developing and implementing these standards is essential to ensuring that future HM trials uphold both methodological validity and ethical legitimacy.

Strengths and limitations

This study has several limitations inherent to qualitative research. Although qualitative interviews provide in-depth and contextually rich insights, the findings are not intended for statistical generalization but may offer transferable insights to similar research contexts. The relatively short duration of some interviews may have limited the depth of individual narratives, despite achieving thematic saturation. Variability in participants’ professional roles may also influence the range of perspectives represented. Interpretation, though inherently subjective, was treated as a source of analytic depth through reflexive engagement, and this subjectivity was managed through verbatim transcription, team-based cross-checking of codes, and reflexive documentation throughout the analytic process. Nevertheless, as with most qualitative studies, the interpretations remain situated within the cultural and institutional context of Chinese herbal medicine research, which may affect their transferability to other settings.

Despite these limitations, this study makes significant contributions to HM research by highlighting overlooked aspects of placebo usage. As the first qualitative research specifically focused on HM placebos, it opens new avenues for understanding and improving HM placebo use. This foundational work sets the stage for future research and applications in HM placebo formulations. Another major strength of the study is its comprehensive inclusion of various roles involved in clinical trials. By integrating perspectives from a diverse range of stakeholders, including doctors, patients, nurses, CRAs, CRCs, pharmaceutical staff, nursing aides, and medical students, the study offers a holistic view of the attitudes and considerations surrounding placebos in HM trials. This wide-ranging inclusion enhances the depth and breadth of insights, providing a robust understanding of the complexities in placebo implementation across different stakeholders.

Conclusion

This study provides valuable insights into the complexities and ethical considerations surrounding the use of placebos in HM clinical trials. The findings highlight diverse understandings of HM placebos across stakeholder groups and professional experiences, reflecting differences in exposure to research ethics and clinical practice. Addressing these gaps through standardized guidelines, improved educational resources, and transparent communication about placebo composition is essential to maintain ethical standards and scientific rigor in HM trials. Future research should focus on refining placebo design and evaluation protocols to enhance trial quality and ensure consistent application across the field of clinical pharmacology.

Abbreviations

CRA

Clinical Research Associate

CRC

Clinical Research Coordinator

HM

Herbal Medicine

RCT

Randomized Controlled Trial

COREQ

Consolidated Criteria for Reporting Qualitative Research

Authors’ contributions

YL conducted the formal analysis, created the visualizations, and drafted the manuscript. XZ contributed to the methodology, investigation, and software development. BQ, XP, and JG participated in the methodology and contributed to reviewing and editing the manuscript. CZ was responsible for conceptualization, methodology, supervision, funding acquisition, and reviewing and editing the manuscript. All authors read and approved the final manuscript.

Funding

This study was supported by Beijing Municipal Natural Science Foundation (Grant No. 7252237), National High-level Chinese Medicine Hospital Clinical Study Specific Funding (Grant No. DZMG-LJRC0008) and Dongzhimen Hospital Project (DZMKJCX-2024-025,CX0158). This funding source had no role in the study design, data collection, analysis, interpretation of data, or manuscript preparation.

Data availability

The interview data is provided in the manuscript and supplementary information files. The original audio recordings of the interviews can be made available upon reasonable request to the corresponding author.

Declarations

Ethical Approval and consent to participate

This study was conducted in accordance with the Declaration of Helsinki. It was approved by the Ethics Committee of Dongzhimen Hospital, Beijing University of Chinese Medicine, China (Approval Number: 2022DZMEC-352-02). All participants were informed of the study’s purpose, procedures, and their rights before participation, and provided written informed consent.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.