Overcoming Barriers for Clinical Research of Acupuncture

Abstract

Acupuncture is increasingly being used in the management of a wide range of symptoms. Despite decades of acupuncture research, a significant gap remains in translating evidence into specific and clear clinical guidelines for acupuncture practice. In this article, the authors discuss the gap between acupuncture research and clinical practice and exploring options to overcome the limitations of current clinical research of acupuncture.

Introduction

Acupuncture is an important adjunct in a patient's cancer care plan for symptom management. The majority of U.S.-based comprehensive cancer centers offer acupuncture.¹ The National Comprehensive Cancer Network clinical care guidelines for supportive care recommends the use of acupuncture for various cancer- or therapy-related symptoms.² Although there has been an increasing body of evidence reporting on acupuncture research in recent decades, a significant gap exists in translating evidence into specific and clear clinical guidelines for acupuncture treatment in the clinical setting.

The lack of understanding of the relationship between presenting symptoms and defined syndromes within Traditional Chinese Medicine (TCM) theory might contribute to differences in acupuncture approaches between the research and clinical setting, such as acupuncture point selection and the type of stimulation used in research designs. The majority of clinical trials use a fixed-point approach for certain symptoms versus the conventional clinical practice of acupuncture that uses a more individualized approach based on constitutional diagnoses and TCM syndromes. In addition, the knowledge gap of the biophysiologic mechanisms of acupunctures effect presents an outstanding challenge in choosing appropriate comparators for acupuncture. Overcoming these barriers is essential to bridge the gap between acupuncture research and practice.

This review discusses the different approaches used in acupuncture research and clinical practice, the underlying principles for each, and the challenges that are faced in the majority of acupuncture research design limiting the contribution to clinical practice. Opportunities in integrating more patient-centered approaches of classical TCM theory and modern precision medicine to improve the clinical applicability of research evidence is discussed.

Discussion

Methodologic differences between acupuncture research and clinical practice

Similar to conventional Western medical practice that uses a patient-centered approach, the formulation of a treatment plan in the clinical practice of acupuncture that follows TCM principles is based on constitutional diagnoses rather than a single symptom. This suggests that 2 patients with similar presenting symptoms may receive a different treatment approach based on constitutional and syndrome-based imbalances. However, acupoint selection and the choice of stimulation in the majority of acupuncture research by randomized controlled trials uses prefixed points targeting a single or multiple symptoms with no variation between patients regardless of the presenting TCM constitutional or syndrome-based presentation.^3–7 Although there may be some overlap in points used within the 2 models, the lack of individualization makes translation between the 2 limited. For example, in the treatment of chemotherapy-induced nausea and vomiting, most clinical trials would use PC6 and ST36. Although these 2 points would most likely be used in the clinical setting, other points would also be added based on the TCM diagnosis of the patient. This lack of treatment individualization in the research setting, which is an important feature of the TCM practice principle, limits the potential benefits that can be derived from acupuncture research and may result in the reduced application of acupuncture research findings in real-life TCM acupuncture practice.

The challenge is that a single symptom may not accurately represent a specific pathologic process that may present with a constellation of symptoms. For example, fever can be a presentation of malignancy as well as infection. A treatment plan for fever depends upon the underlying pathophysiology, not the symptom of fever alone. Similarly, acupuncture point selection for the treatment of cancer-related fatigue will vary in the clinical setting based on excess of heat versus diminished Qi, and using a fixed-point approach separate from TCM constitutional or syndrome-based presentation may have limited benefit.

Further complicating the situation is that different acupoint selections for the same symptom are often used in acupuncture research for symptom management. For example, a study by Cho et al. found that manual acupuncture improved quality of life in cancer patients with radiation-induced xerostomia using the acupuncture points of ST 6 (Jiache), LI 4 (Hegu), ST 36 (Zhu San Li), and SP 6 (San Yin Jiao) based on the TCM theoretical mechanism of supporting Yin (Water-like) elements to increase salivary production.⁸ However, others have selected different acupuncture points in their research, primarily based on previous publications with or without consideration of TCM theoretical reasoning, for the same symptom.^9,10

Methodologic heterogeneity in acupuncture research is recognized as a major contributor to the often equivocal and even conflicting findings.^3,4 Many of the differences in intervention methods are intrinsic to the clinical practice of acupuncture that primarily follows principles of TCM, of which the pathophysiologic foundation for diagnosis is radically different from that of conventional Western medicine. In a retrospective review of acupuncture practice in a large tertiary cancer center, Liu et al. showed that TCM diagnoses varied widely among patients with the same primary presenting symptom and the acupuncture treatment plans (e.g., acupoint selections) correlated significantly with TCM diagnoses.¹¹ Research findings have mirrored this highly individualized acupuncture approach and indicate that TCM diagnosis may be predictive of acupuncture treatment response.^12,13

Few studies have actually compared using the fixed-point approach versus a more individualized approach that is used in clinical care. The appeal of using fixed points based on specific symptoms is that it is easy to replicate in the clinical research setting. The challenge of the more individualized approach is that the basis of the individualization—the TCM diagnosis—does not have a gold standard for assessment and subsequent prescribing. TCM diagnosis is complex and made up of constitutional assessments, symptoms, pulse, and tongue evaluation, to name a few. Unlike using strictly objective outcomes such as thyroid stimulating hormone (TSH) and thyroxine (T4) levels to diagnose and treat a thyroid condition, TCM diagnostic strategies are more subjective, leading to variation between practitioners and making replication more challenging for a research setting.

Although some laboratories have tried to develop systematized strategies to more objectively assess TCM diagnosis and subsequent prescribing practices,¹⁴ including the development of technologies for tongue and pulse assessment,^15–18 little research has evolved in this area. Developing strategies to more objectively assess TCM diagnosis and point selection will improve the transition of research into clinical practice. Instead of targeting a single symptom, clinical acupuncture research that addresses a specific pathophysiologic cause may be more profitable in providing explicit guidance on the real-world practice of acupuncture.

Mechanisms of acupuncture and selecting appropriate comparators for clinical acupuncture research

The location of acupoints and meridians on the body surface has been well documented in classical TCM acupuncture books dating back as far as 2100 years ago. The classical TCM theory considers acupuncture meridians a network of channels, with large (Jing) channels being connected through small (Luo) channels. However, there was little scientific proof of the existence of acupuncture meridians until 1963, when Kim used scintigraphic imaging and suggested that acupuncture meridians were unique connective tissue channels.¹⁹ These channels were later visualized with isotope tracing and histologic staining studies.^20,21 In fact, recent research by Langevin et al. hypothesized^22,23 that it is the connective tissue manipulation through the “grasp” of the needle by the fascia and subsequent stimulation that transmits a mechanical signal to connective tissue cells through mechanotransduction.²⁴ Further physiologic studies revealed that acupoints and meridians had lower electrical resistance, altered acoustic conduction, and higher skin potential, compared with surrounding tissues that were not on the meridians.^25–27 Consistently, Li et al.'s histologic study of acupoints suggests that they are excitable muscle/skin–nerve complexes with high density of nerve endings.²⁸ Furthermore, Silberstein theorized that acupoints and meridians are a cutaneous intrinsic visceral afferent nervous system that is part of the autonomic nervous system along with the sympathetic, parasympathetic, and enteric nervous systems.²⁹

The concept that the acupoints and meridians are part of the autonomic nervous system may help explain the broad biophysiologic effects of acupuncture that have been reported. Acupuncture treatment has been found to regulate anxiety, pain perception, blood pressure, gut motility, uterine contractions, glucose metabolism, glucocorticoids, and sex hormones through modulation of the sensory and autonomic nervous systems peripherally and centrally.¹

The daunting complexity of acupuncture mechanisms presents great challenges for clinical acupuncture research. The lack of a thorough understanding of the mechanisms of acupuncture makes it a challenge to choose appropriate control groups. Many have challenged the appropriateness of sham acupuncture as a placebo control for real acupuncture.^30,31 Sham comparators are intended to be less physiologically active than the real treatment but may not be inert, whether or not the skin is actually punctured. In addition, the sham technique cannot be blinded to acupuncturists and may not be indistinguishable to participants who have received previous acupuncture. Many other components of acupuncture such as number of needles used, needle size, level of insertion, intensity and type of needle stimulation, retention time, as well as frequency and duration of treatments differ among research designs, and can contribute to divergent research findings. In addition to other limitations, sham acupuncture may not be always a practical research design, as it will lead to large sample sizes due to a robust placebo effect.³² Choosing widely accepted conventional medicine symptom management approaches, both pharmacologic or nonpharmacologic interventions, as controls and examining equivalence may be more appropriate to assess the efficacy of acupuncture for symptom management.

Opportunities to close the gap

Despite the significant differences in describing pathophysiologic processes of various diseases between TCM and Western medicine, both medical principles make treatment decisions based on diagnoses and coexisting complications. Although a fixed-acupoint study design is easy to replicate, selecting a suitable cohort that is appropriate for the predetermined treatment will likely produce disease-specific and practice-relevant evidence that will improve real-world application. Incorporating TCM diagnosis in the research design of fix-point studies will help gather relevant research to at least correlate outcomes with diagnosis. The use of pragmatic study designs that base acupoint selection according to TCM diagnosis attempting to mimics an actual practice setting may prove helpful and is starting to be used more frequently in recent randomized controlled studies.³³ Developing gold-standard, replicable, and reliable strategies for TCM diagnosis and treatment is essential for this research design and to conduct clinical trials that better mimic real-world clinical setting use of acupuncture.³⁴ The more individualized approach will allow for a more authentic assessment and documentation of the true potential for acupuncture to treat various conditions.

Conclusions

To overcome methodologic challenges in acupuncture research, future collaborative efforts are needed to (1) improve understanding of the relationship of the physiologic and pathophysiologic foundations of TCM diagnostics with those of Western medicine; (2) consider TCM diagnosis in study cohort selection, subgrouping, and post hoc analyses; (3) develop replicable objective techniques for TCM diagnosis; (4) reach consensus on an appropriate acupuncture intervention for a specific TCM diagnosis or syndrome and develop individualization algorithms that are replicable; and (5) consider comparators, including medications, physical therapy, and mind and body modalities that are considered standard of care or appropriate alternatives for symptom control.

Author Disclosure Statement

No competing financial interests exist.

Funding Information

No funding was received for this article.