Interpretation of Good Clinical Practice of Acupuncture and ... : Guidelines and Standards in Chinese Medicine (2025)

In 2010, Chinese Acupuncture and Moxibustion were inscribed on the UNESCO Representative List of the Intangible Cultural Heritage of Humanity, which signifies that the international community has culturally recognized these practices. However, the promotion of acupuncture and moxibustion around the world faces the ongoing challenge of insufficient evidence to prove their effectiveness.

According to the report on difficulties faced by member countries of the WHO Traditional Medicine Strategy, the absence of research data remains the primary difficulty in the development and application of traditional medicine transmission, which is in apparent conflict with the proliferation of clinical studies on acupuncture in recent years, suggesting that what is lacking in clinical studies on acupuncture is high-quality clinical evidence. The primary goal of improving the quality of evidence in acupuncture clinical studies is to design acupuncture clinical studies that are consistent with the characteristics of acupuncture, and that can be recognized internationally. Currently, the International Conference on Harmonization Good Using Practice (GCP)¹ and Chinese GCP promulgated by the National Medical Products Administration² and other guidelines play an essential role in safeguarding the quality and level of evidence in clinical research on medicines, which has become the code of conduct for clinical research. However, it is not entirely appropriate to adopt drug GCP requirements for acupuncture clinical studies owing to the complexity of acupuncture clinical research and its unique features. In this context, Good Clinical Practice of Acupuncture and Moxibustion Research Management (ACU-GCP) was proposed and written by the Key Research Center of Clinical Evaluation Methods of Traditional Chinese Medicine, State Administration of Traditional Chinese Medicine, China Academy of Traditional Chinese Medicine. The standardization aims to improve the quality of acupuncture clinical research, enhance the credibility of the results, make the results of acupuncture clinical research more truthful, accurate, and reliable, and protect the rights and interests of participants in acupuncture clinical research.

Over the past decade since the release of ACU-GCP, the number of global publications related to acupuncture clinical trial literature has generally exhibited an upward trend, with 52 original clinical research articles on acupuncture published in internationally recognized journals across 9 countries, including 31 articles (31/52) authored by the Chinese team (59.62%)³. In contrast to previous years, the number of high-quality acupuncture clinical studies in China has steadily increased over the past decade, from nearly none before 2015 to ∼5–6 studies per year. This partially reflects the role of ACU-GCP in enhancing both the quantity and quality of acupuncture clinical studies; however, there is still an urgent need for high-quality evidence because of the need for international dissemination of acupuncture. An analysis of the last 10 years of clinical randomized controlled trials on acupuncture revealed that many trials adhered to the ACU-GCP requirements just regarding the safety evaluation of adverse events in clinical trials, but not throughout all phases of the trial^4–6. This indicates a problematic application of ACU-GCP, potentially stemming from a lack of understanding of the guidelines by clinical researchers.

This article will introduce and explain the key points of the ACU-GCP to help researchers understand better and apply the reporting standard as well as to promote the dissemination of ACU-GCP, furthermore promoting the standardization of the protection of the rights and interests of the participants in research, the design, implementation, and reporting of clinical research, as well as the management of related institutions and personnel, to improve the quality of Acupuncture and Moxibustion Clinical Research.

The process of developing the ACU-GCP

The ACU-GCP serves as a code of research activity, both a cognitive and a social standard. It encompasses the standardization of acupuncture clinical research practice techniques, practice activity management, and ethical conduct of scientific research. Focusing on the key issues of quality management, adherence control, blinded implementation, controlled implementation, and staging of acupuncture clinical studies, the expert consensus methodology was adopted, and 13 rounds of consultation were conducted, 326 people were involved in the work, and 17 revisions were made, culminating in the final ACU-GCP submission for review, which was published on July 25, 2014. Three clinical research^7–9 in an international multicenter clinical evaluation study of acupuncture efficacy supported by “key projects” in the National Science and Technology Pillar Program during the 12th five-year plan period were tracked entirely to analyze the feasibility and usefulness of ACU-GCP content in practical applications found that the content of the entries in ACU-GCP is applicable to guide practice.

Interpretation of entries of ACU-GCP

General provision

The general provisions of ACU-GCP encompass its objectives, purposes, and fundamental principles. The ACU-GCP is designed to protect the rights and privacy of patients and research subjects. The research results are accurate accurately reflect the unique characteristics of acupuncture so that the rights and interests of research subjects can be safeguarded. The research conclusions are reliable, providing a foundation for the transparent measures of regulating the whole process of information of clinical research on acupuncture and defining the qualification and scope of work of clinical researchers of acupuncture. ACU-GCP applies to each phase and type of acupuncture clinical studies.

Organizational management

The organization and management of clinical studies are an integral part of the overall quality control process, and the ACU-GCP mandates that the sponsoring organization of acupuncture clinical studies be responsible for selecting and hiring study leaders, approving study budgets, providing funding, monitoring study progress, and evaluating and accepting study results. It also stipulates that the process of acupuncture clinical research includes project identification, team formation, programmatic design, protocol development and ethical review, study implementation, data collection, statistical analysis, report writing and publication, and in multicenter studies should also include organizational training, preclinical studies, data management, and quality management. The institution initiating the research should refer to the ACU-GCP for organizational and process oversight, including contract, funding, archival, and intellectual property management, which will contribute to the research’s authenticity.

Protection of the rights and interests of research subjects

Protecting the rights and interests of clinical research subjects is not only a legal and ethical obligation but also a crucial factor in ensuring the fairness and safety of research while promoting the healthy development of acupuncture clinical research. Acupuncture clinical research protocols should be reviewed and approved by an ethics committee, and written informed consent should be obtained from the study participants. Based on the Declaration of Helsinki’s Basic Principles of Clinical Research Ethics and Medical Ethics¹⁰, the ACU-GCP requires that ethics committees for acupuncture clinical research protocols should include acupuncture professionals or independent acupuncture consultants to provide targeted advice on safeguarding the rights and interests of research subjects during the design of acupuncture clinical trials. ACU-GCP emphasizes that informed consent should describe the possible alternative treatments and their procedures or processes to protect the patient’s rights. Furthermore, real-world acupuncture clinical studies are also subject to review and approval by ethics committees that focus on safeguarding private information.

Research design

Acupuncture clinical research design primarily includes medical, statistical, ethical, and management designs. The research components should be based on the purpose of the study and the actual clinical problem; subsequently, an appropriate clinical research hypothesis should be established, which can be designed according to the maturity of the intervention program. Compared with medications, acupuncture interventions encompass more procedures and dimensions, including acupoints or stimulation sites, stimulation methods, acupuncture effects, etc. The interventions inevitably involve interactions between the acupuncture operator and the subject, which can influence patient compliance and treatment effects¹¹. Therefore, intervention methods and observational indicators, should be carefully selected in the study design. The statistical analysis should also account for the influence of the acupuncture procedure on the study design, sample size, and effect assessment. ACU-GCP recommends specialized training, assessment, and quality control measures of field operations for researchers, acupuncture operators, and indicator assessors. The protocol clearly describes and specifies the localization methods, operation techniques, and instrument specifications for each acupuncture point, and the use of relevant international, national, or industry standards is encouraged whenever possible. In addition, appropriate management measures should be implemented to ensure the comparability of the baseline data and the reliability of the study results.

The ACU-GCP proposes that the selection of interventions for the control group in acupuncture clinical studies should provide the specific methodology, the basis for the selection, and the source. Currently, sham acupuncture serves as a critical control modality for evaluating the effects of acupuncture in clinical studies of acupuncture¹². The challenge in the designing of sham acupuncture is not only to note whether its effects differ from those of the intervention group but also to ensure blinding. Using an optimized study design for sham acupuncture controls in high-quality acupuncture clinical studies can help achieve a balance between the two perspectives. For instance, sham acupuncture can be categorized as stabbing and nonstabbing. A study evaluating the difference between the effects of needling and sham needling on methadone reduction used nonstabbing blunt-tipped needles as the intervention in the sham needling group¹³. As a masked study, the team designed a comfort device for both the needling and the sham-needling groups, which used either a sharp or blunt-tipped needle loaded into the device’s catheter to achieve different interventions. They also appointed an independent researcher to oversee interactions between the subjects and the physicians to prevent unblinding and address any grouping issues related to their communication. The control group of another clinical study of acupuncture used a piercing sham-needling method with shallow punctures at the same points, which in turn had a more significant physiological effect than the non-piercing sham needles and may have narrowed the difference from the needling group¹⁴. Therefore, ACU-GCP recommends conducting a pilot study may be conducted to determine if the sham acupuncture group achieves the predetermined control effect.

In addition, the needling intervention should give particular consideration to possible risks, formulate appropriate treatment measures for potential situations that may arise during treatment, such as needle fainting, bleeding from needle holes, blistering of the skin, etc, and especially formulate appropriate treatment plans for possible accidents such as needling in hazardous areas, as well as draft appropriate informed consent forms according to the characteristics of the populations of different stages of the clinical study of acupuncture and moxibustion.

Clinical protocols

Acupuncture clinical protocols are the basis for acupuncture clinical study training, implementation, quality control, supervision, inspection, and disclosure of information on acupuncture clinical studies. The clinical study protocol is the foundation of the study design and is a key determinant of the quality of the clinical study. The ACU-GCP provides the essential elements for reference in clinical study protocols. After the ethics committee approves, the protocol should be registered with an international or national public institution¹⁵. Meanwhile, it is recommended that the research program be publicly published in relevant journals to increase its hyalinization and research content, which can help researchers to fully consider the scientific, ethical requirements, and safety aspects of a trial before it begins, and to be subject to public scrutiny during and after the trial.

An investigator’s brochure and a participant’s manual should be developed to guide the conduct of the study. The investigator’s brochure is a compilation of research protocols, training programs, and clinical and non-clinical information related to clinical research. The participant’s manual introduces the basic information about the clinical research study in which they are participating, the content of their participation, and the obligations and rights of the participants. The ACU-GCP regulates the content of the investigator’s brochure and the participant’s manual to improve the standardization of investigator manuals and participant handbooks and to ensure that investigators and participants understand the characteristics and potential risks of acupuncture trials. It also helps to ensure that the trial process follows the PROTOCOL and to manage the trial process promptly, especially risk regulation and assessment of adverse reactions.

Qualifications and responsibilities of relevant personnel

The personnel involved in acupuncture clinical research generally include investigators, research coordinators, assistant investigators, clinical investigators, acupuncture operators, index evaluators, statisticians, quality managers, data managers, financial personnel, and research administrators. The division of labor among the various categories of personnel is clearly defined, and they should have the appropriate professional and technical titles necessary for their roles. The personnel must be trained and certified in the research program and are required to perform in accordance with the program’s standards. The ACU-GCP describes in detail the responsibilities and job content of the above personnel.

Among them, the acupuncture operator is a key part of the acupuncture clinical trial and has an essential influence on the whole clinical trial process. Therefore, the ACU-GCP outlines detailed requirements for the training of acupuncture operators. The training process and assessment in acupuncture clinical studies should be tailored to the specific research content and clearly articulated in published articles, especially in multicenter studies. For example, a multicenter randomized controlled trial of acupuncture¹⁶ that has been published in Clinical Medicine not only specified the work experience of the acupuncture operator but also the details of the needling operator’s workflow and “de qi” stipulated to ensure the consistency and safety of the multicenter treatment. Training and regulations for acupuncture practitioners not only reduced the central effect in the study, but also enhanced the article’s persuasive power through detailed descriptions.

Like the quality assurance system for drug clinical trials, acupuncture clinical studies should have specialized personnel for monitoring, auditing, and inspection responsible for multiple monitoring levels to ensure the study is conducted according to the protocols. The ACU-GCP describes the job duties and responsibilities of the study manager, ombudsman, auditor, and inspector. It should be emphasized that the inspections include not only the routine clinical trial process but also focus on monitoring authenticity, standardization, and adherence to the implementation of protocols.

Quality management

ACU-GCP requirements for quality management of acupuncture clinical research are specific. The accuracy of acupuncture procedures, along with the truthfulness and reliability of assessing and recording each index, are the key issues for the quality management of acupuncture clinical research. All investigators and acupuncture operators should receive on-site, and elaborate training materials and assessments should be developed to ensure the training is practical and detectable. A 4-tiered internal quality control system, including monitoring, auditing, and inspection, is recommended for extensive acupuncture clinical studies. The ACU-GCP provides detailed descriptions of the quality control process, and the main idea is to investigate, monitor, and trace every process and record of study operations, data generation, recording, and reporting programs. The ACU-GCP also recommends establishing clear and effective quality control methods for real-world acupuncture clinical studies. Although the internal quality control process rarely is featured in published research reports or articles, establishing and rigorously implementing an institutionalized internal quality control system is an essential guarantee that acupuncture clinical studies will be conducted as designed.

Data management and statistical analysis

Data management in acupuncture clinical research is an integral part of quality control. ACU-GCP emphasizes that documentation and information should be preserved throughout the data cleansing process to make data transparent and traceable. Proper randomization protocols and third-party data management are crucial for ensuring blinded implementation and maintaining data quality control in extensive multicenter studies. There are many methods of randomization in acupuncture clinical research, and it is necessary to adopt a suitable randomization scheme according to the sample size and the purpose of the study. Utilizing a centralized randomization system enhances control over allocation and concealment and is also beneficial for quality control and shortening the cycle time of clinical research¹⁷. With the establishment and continuous improvement of various clinical research data platforms, it is common to adopt computerized systems for data management, and intelligent systems combining artificial intelligence and big data can improve the efficiency of data management and statistics in clinical research^17–20. Computerized data management also poses challenges for data security. It is essential to adhere to data security laws and regulations throughout the study to safeguard clinical data. The system and the operating environment should be secured regarding software and hardware, and the system personnel should be trained and qualified. The system should have essential functions such as rights management, trace auditing, data backup, etc, to further guarantee the research data’s authenticity. The database design should also follow international, national, and industry-standard terminology specifications to meet data interoperability and communication needs in various situations.

Selecting a statistical strategy that aligns with the study’s objectives and the data’s characteristics can provide better answers to the clinical questions posed by the study. The assessment of the effects of acupuncture as a complex intervention is influenced by multiple factors. In addition to quality control during the study protocol and operations, selecting reasonable outcomes, clarifying their clinical significance, and specifying appropriate statistical analysis methods and models are also essential to reduce false positives or negatives. In a randomized controlled trial of acupuncture for the treatment of chronic spontaneous urticaria published in Annals of Internal Medicine²¹, linear regression models were used to assess the primary and some of the secondary outcomes, with Bonferroni adjustment applied to reduce the risk of type I error from multiple comparisons. It is also important to note that shedding is unavoidable during the actual study, and even compared with drug clinical trials, acupuncture clinical studies may result in poorer participant adherence due to more frequent treatments and pain during treatment, therefore, missing values should be addressed using appropriate statistical methods. The ACU-GCP suggests that a statistical analysis plan should be developed in advance during the design phase of a clinical study, including specific analytical metrics and statistical analysis methods. Changes made during the analysis should also be justified.

Reports of clinical study

Irrespective of the results and whether the study is completed, a clinical study report should be submitted to the corresponding department at the end of all acupuncture clinical studies. Reporting negative results or incomplete clinical studies contributes to reducing the waste of resources in the same trials and minimizing publication bias to avoid misleading researchers and policymakers. It is also ethically beneficial to safeguard the rights of the participants in the potentially adverse effects of incomplete acupuncture clinical trials resulting from negative results. The clinical study report should pay special attention to the authenticity of the results and the reliability of the study conclusions. The ACU-GCP encourages acupuncture clinical trials to publish their results and findings publicly, and the publication should indicate the registration number. The content of the clinical study report may follow the categories outlined in the ACU-GCP and should refer to the recommended reporting specifications based on the type of study, including the STRICTA²², QUOROM,²³ etc. Clinical study registration and disclosure of study reports can improve the hyalinization of acupuncture clinical studies, which is conducive to enhancing the authenticity of the studies and protecting the rights of the subjects, thus contributing to improving the quality of acupuncture clinical studies.

Nomenclature

The ACU-GCP specifies a total of 24 terms, including clinical trial/study of acupuncture and moxibustion, manipulator of acupuncture and moxibustion, efficacy, effectiveness, clinical study design, Independent Ethics Committee, Institutional Review Committee, adverse reactions of acupuncture and moxibustion, adverse events, real-world study, elements of a clinical research, case report form, compliance, bias, GCP, independent data and monitoring committee, informed consent, subjects/trial subject, medical institution of acupuncture and moxibustion clinical study, quality management, standard operating procedures, and hyalinization of clinical research.

First, the ACU-GCP defines the concept of an acupuncture clinical trial/study as any study conducted on human subjects to discover or confirm the clinical efficacy of acupuncture treatment and/or determine any adverse effects, safety, and/or effectiveness of acupuncture treatment. This includes traditional acupuncture treatments as well as new acupuncture treatments that have been developed in recent years. The concepts of acupuncture efficacy and effectiveness need to be distinguished, with efficacy emphasizing the self-reliance of the intervention under ideal conditions and reflecting the net effect of the intervention. In contrast, effectiveness is the combined effect of efficacy and the condition and level of health care services under actual conditions. The concepts of clinical study design, Independent Ethics Committees, and Institutional Review Boards are rephrased in the terminology section, highlighting the importance of Independent Ethics Committees and Institutional Review Boards for acupuncture clinical research.

Adverse reactions and adverse events in clinical studies of acupuncture are essential components for evaluating in the evaluation of the effects of acupuncture in clinical research and as well as for protecting participants’ rights. They are emphasized in the definitions in ACU-GCP. Acupuncture adverse reactions mainly refer to the occurrence of harmful reactions unrelated to the therapeutic purpose during the whole process of regular acupuncture manipulation and intensity, and the adverse events emphasize the identification of the existence of association with acupuncture treatment. The ACU-GCP outlines the significance of real-world acupuncture clinical research and highlights its distinction from ideal-world clinical research. The remaining terminology is derived from the results of expert consensus, and reference to the GCP of drug screening is the terminology that meets the requirements of this specification and can provide a reference for acupuncture clinical researchers.

Discussion

The international interest in acupuncture is driving a growing trend in its research. Still, clinical studies of acupuncture differ significantly from those of pharmaceuticals, as they do not adhere to standard clinical research protocols, resulting in published studies of varying quality. Some international studies have even concluded that acupuncture has no therapeutic effect, a finding that lacks rigor^24,25. Against this background, the ACU-GCP emerged, highlighting the characteristics of acupuncture and moxibustion. ACU-GCP focuses on key issues such as organizational management, protection of the rights and interests of research subjects, study design, and quality control, and attempts to provide standards and management basis for the whole process of acupuncture clinical research. In the compilation process, the project team engaged in extensive discussions and multiple rounds of consensus-building with both domestic and international experts, from establishing the framework to defining terms. The verification of real projects also ensures the scientific validity and practical applicability of the ACU-GCP. This article interprets the ACU-GCP to help readers understand the content and apply it to the practice, ultimately improving the quality of acupuncture clinical research.

Acknowledgments

The authors express gratitude to the funding sources that supported their research, as well as to all the reviewers and editors for their dedication and time invested in their work.

Statement of ethics

This study did not involve human or animal subjects, so ethical approval was not required. The study protocol adhered to the guidelines established by the journal.

Conflict of interest disclosure

The authors declare no competing interests.

Funding source

This study was supported by Beijing Traditional Chinese Medicine Science and Technology Development Foundation, Chinese Medicine Treatment of Ovarian Reserve Hypoplasia: A Real World Case Registry Study (BJZYYB-2023-74). China Academy of Traditional Chinese Medicine (CATCM) balance fund reestablishment project, The Key Technology of Real World Case Registration Study (2022031). Science and Technology Innovation Project of the Chinese Academy of Traditional Chinese Medicine, CI2021A05408.

Data availability statement

Data availability does not apply to this article as no new data were created or analyzed in this study.

Author contributions

Y.T.: wrote the paper. M.W. and X.C.: revised the manuscript. L.H.: designed the research. B.L.: provided study oversight. J.L.: provided final content.

References