Acupuncture—A Question of Culture... and of skill to induce impression of being effective :-)

Acupuncture—A Question of Culture. Matthias Karst, Changwei Li. JAMA Netw Open. 2019;2(12):e1916929. Dec 6 2019, doi:10.1001/jamanetworkopen.2019.16929

By the end of radiotherapy for head and neck cancers, more than 50% of patients experience radiation-induced xerostomia (RIX), a condition manifested by a long-lasting perception of dry mouth. Radiation-induced xerostomia is associated with a series of complications, such as difficulty sleeping and speaking, dysgeusia, and dysphagia, that significantly affect patients’ quality of life. A 2019 review of clinical trials1 compiled several strategies against RIX and reported that sialogogue medications, sparing parotid glands by intensity-modulated radiation therapy, and salivary gland transfer have been shown to be effective but at the cost of adverse events or persistent symptoms after treatment. A 2015 randomized clinical trial2 demonstrated that patients with RIX who received acupuncture-like transcutaneous electrical nerve stimulation had marginally better responses and significantly fewer adverse events compared with patients who received oral pilocarpine. This trial suggested that acupuncture may be a promising approach to prevent RIX.

In the study by Garcia et al,3 results of a 2-center, phase 3, randomized, sham-controlled clinical trial for the treatment and prevention of RIX with acupuncture are presented. Interestingly, one center was situated in the United States, and the other was in China. A classic 3-arm study design was used to compare true acupuncture (TA) and sham acupuncture (SA) with a standard care control (SCC). Compared with SCC, TA resulted in significantly lower xerostomia scores and lower incidence of clinically significant xerostomia 1 year after treatment, while the SA was not significantly associated with improved xerostomia scores. However, no significant difference between TA and SA xerostomia scores was observed, and both acupuncture groups combined showed significantly lower xerostomia scores compared with SCC. This phenomenon is often found in acupuncture trials and may be resolved by the increase of the overall sample sizes or, at least, by the disproportionate increase of the size of the TA group to detect differences between TA and SA.

One of the significant and exciting findings in the study by Garcia et al3 is the differences between the US and Chinese study sites. Among US patients, only the SA group showed a significantly better xerostomia score compared with the SCC group, while no differences were observed between the TA and SCC groups. In contrast, among Chinese patients, TA significantly improved the xerostomia scores compared with SA and SCC, while the SCC and SA had very similar efficacy. In other words, the Chinese study population clearly showed a hypothesis-confirming result, while the US study population seemed to have been more susceptible to SA. This finding coincides with the opposite tendency of the expectation scores during the course of the treatment: in the Chinese patients, confidence in the sham treatment decreased, while US patients built more confidence in the sham treatment through time. In China, most patients are well aware that without the de qi sensation, acupuncture treatment does not work. Acupuncture service has a very low price and is widely available in most community health care centers and hospitals in China.4 Therefore, Chinese acupuncturists have to have proficient needle manipulation skills to quickly elicit strong and long-lasting de qi sensations; otherwise, patients may switch to other acupuncturists. This may also explain the larger effect size of TA in the study site in China.

Usually in acupuncture trials, SA consists of using real acupuncture needles and inserting them superficially at non–acupuncture points (minimal acupuncture). In this study, SA consisted of a mixture of real and nonpenetrating placebo needles and a mixture of real and sham points. In addition, in the informed consent process, patients were told that 2 different acupuncture approaches would be used but that 1 approach might not target dry mouth symptoms. Although this aspect of the informed consent process was intended to maximize confidence in both acupuncture approaches, apparently in the Chinese setting characterized by a long cultural background of traditional Chinese medicine (TCM), SA was experienced differently compared with TA. In this setting, Chinese clinicians are deeply familiar with TCM and acupuncture. Therefore, they may have felt more irritated using the SA procedure, a suggestion that they may have carried over to their patients. In contrast in Western societies, TCM and acupuncture are much less deeply rooted, which likely resulted in more uncertainties on specific acupuncture treatments. Given the nature of SA, it might be a reasonable way to use the same acupoints as in TA but manipulate needles in a countertreatment manner. For example, if the treatment protocol requires “tonifying energy” in an acupoint, the SA could “sedate energy” at the same acupoint. However, this is unethical for acupuncturists, as they believe that such treatment would worsen the condition being treated.

Findings in the study by Garcia et al3 support the idea that acupuncture exerts its effects not only or not mainly by needle site activity and specific neurophysiological mechanisms but also by expectations, conditioning, and suggestibility of clinicians and patients.5 The effects of these unspecific factors may be quite large. Together with many other 3-arm acupuncture trials in Western countries, results of the study by Garcia et al3 has disclosed what is referred to in the literature as the efficacy paradox,6 that is, even though TA and SA were similarly effective, the size of overall effect of any acupuncture was superior to standard therapy.

In a previous randomized, single-blind, placebo-controlled, multifactorial, mixed-methods clinical trial on chronic pain, the personality of individual practitioners (not the empathic behavior) and patient’s beliefs about treatment veracity independently had significant effects on outcomes.7 However, patients and acupuncturists are embedded in a larger cultural context in which acupuncture appears to support the therapeutic ritual of the patient in a unique way and plays a crucial role in the therapeutic outcome of the patient. In support of this, recent research has shown that these complex, ritual-induced biochemical and cellular changes in a patient’s brain are very similar to those induced by drugs.8

With these ideas in clinical acupuncture trials in mind, the cultural background should increasingly move to the center of attention. What was predicted in a small interview among patients with back pain came true: “In China, outcomes of active acupuncture will be still better than the outcomes of sham acupuncture.”9



Garcia et al.'s work, reference 3:

Effect of True and Sham Acupuncture on Radiation-Induced Xerostomia Among Patients With Head and Neck Cancer: A Randomized Clinical Trial. M. Kay Garcia et al. JAMA Netw Open. 2019;2(12):e1916910. Dec 6 2019, doi:10.1001/jamanetworkopen.2019.16910

Key Points
Question  Can acupuncture prevent radiation-induced xerostomia, an adverse effect among patients with head and neck cancer undergoing radiation therapy?
Findings  In this randomized clinical trial with 339 participants, 12 months after the end of radiation therapy, the xerostomia score of the true acupuncture group was significantly lower than that of the standard care control group.
Meaning  These findings suggest that acupuncture should be considered for the prevention of radiation-induced xerostomia, but further studies are needed to confirm their clinical relevance and generalizability. 

Abstract
Importance  Radiation-induced xerostomia (RIX) is a common, often debilitating, adverse effect of radiation therapy among patients with head and neck cancer. Quality of life can be severely affected, and current treatments have limited benefit.
Objective  To determine if acupuncture can prevent RIX in patients with head and neck cancer undergoing radiation therapy.
Design, Setting, and Participants  This 2-center, phase 3, randomized clinical trial compared a standard care control (SCC) with true acupuncture (TA) and sham acupuncture (SA) among patients with oropharyngeal or nasopharyngeal carcinoma who were undergoing radiation therapy in comprehensive cancer centers in the United States and China. Patients were enrolled between December 16, 2011, and July 7, 2015. Final follow-up was August 15, 2016. Analyses were conducted February 1 through 28, 2019.
Intervention  Either TA or SA using a validated acupuncture placebo device was performed 3 times per week during a 6- to 7-week course of radiation therapy.
Main Outcomes and Measures  The primary end point was RIX, as determined by the Xerostomia Questionnaire in which a higher score indicates worse RIX, for combined institutions 1 year after radiation therapy ended. Secondary outcomes included incidence of clinically significant xerostomia (score >30), salivary flow, quality of life, salivary constituents, and role of baseline expectancy related to acupuncture on outcomes.
Results  Of 399 patients randomized, 339 were included in the final analysis (mean [SD] age, 51.3 [11.7] years; age range, 21-79 years; 258 [77.6%] men), including 112 patients in the TA group, 115 patients in the SA group, and 112 patients in the SCC group. For the primary aim, the adjusted least square mean (SD) xerostomia score in the TA group (26.6 [17.7]) was significantly lower than in the SCC group (34.8 [18.7]) (P = .001; effect size = −0.44) and marginally lower but not statistically significant different from the SA group (31.3 [18.6]) (P = .06; effect size = −0.26). Incidence of clinically significant xerostomia 1 year after radiation therapy ended followed a similar pattern, with 38 patients in the TA group (34.6%), 54 patients in the SA group (47.8%), and 60 patients in the SCC group (55.1%) experiencing clinically significant xerostomia (P = .009). Post hoc comparisons revealed a significant difference between the TA and SCC groups at both institutions, but TA was significantly different from SA only at Fudan University Cancer Center, Shanghai, China (estimated difference [SE]: TA vs SCC, −9.9 [2.5]; P < .001; SA vs SCC, −1.7 [2.5]; P = .50; TA vs SA, −8.2 [2.5]; P = .001), and SA was significantly different from SCC only at the University of Texas MD Anderson Cancer Center, Houston, Texas (estimated difference [SE]: TA vs SCC, −8.1 [3.4]; P = .016; SA vs SCC, −10.5 [3.3]; P = .002; TA vs SA, 2.4 [3.2]; P = .45).
Conclusions and Relevance  This randomized clinical trial found that TA resulted in significantly fewer and less severe RIX symptoms 1 year after treatment vs SCC. However, further studies are needed to confirm clinical relevance and generalizability of this finding and to evaluate inconsistencies in response to sham acupuncture between patients in the United States and China.