….And no further research is needed.
These 3 excellent articles provide some background for my blog, but their titles alone are worth leading with:
Each of these articles helps highlights an important distinction between an evidence-based medicine versus science based medicine perspective on acupuncture that will be discussed here.
“Acupuncture should be considered as one option for migraine prophylaxis in light of our findings.”
The currently freely accessible article can be found here.
A pay-walled editorial from Dr.Amy Gefland can be found here.
The trial was registered long after patient recruitment had started and the trial protocol can be found here
[Aside: What is the value of registering a trial long after recruitment commenced? Do journal articles have a responsibility to acknowledge a link they publish for trial registration is for what occurred after the trial commenced? Is trial registration another ritual like acupuncture?]
Uncritical reports of the results of the trial as interpreted by the authors echoed through both the lay and physician-aimed media.
Coverage by Reuters was somewhat more interesting than the rest. The trial authors’ claim that acupuncture for preventing migraines was ready for prime time was paired with some reservations expressed in the accompanying editorial.
“Placebo response is strong in migraine treatment studies, and it is possible that the Deqi sensation . . . that was elicited in the true acupuncture group could have led to a higher degree of placebo response because there was no attempt made to elicit the Deqi sensation in the sham acupuncture group,” Dr. Amy Gelfand writes in an accompanying editorial.
Come on, Dr. Gelfand, if you checked the article, you would have that Deqi is not measured. If you checked the literature, even proponents concede that Deqi remains a vague, highly subjective judgment in, this case, being made by an unblinded acupuncturist. Basically the acupuncturist persisted in whatever was being done until there was indication that a sensation of soreness, numbness, distention, or radiating seemed to be elicited from the patient. What part of a subjective response to acupuncture, with or without Deqi, would you consider NOT a placebo response?
Dr. Gelfand also revealed some reasons why she may bother to write an editorial for a treatment with an incoherent and implausible nonscientific rationale.
“When I’m a researcher, placebo response is kind of a troublesome thing, because it makes it difficult to separate signal from noise,” she said. But when she’s thinking as a doctor about the patient in front of her, placebo response is welcome, Gelfand said.
“You know, what I really want is my patient to feel better, and to be improved and not be in pain. So, as long as something is safe, even if it’s working through a placebo mechanism, it may still be something that some patients might want to use,” she said.
Let’s contemplate the implications of this. This editorial in JAMA Internal Medicine accompanies an article in which the trial author suggests acupuncture is ready to become a standard treatment for migraine. There is nothing in the article to which suggests that the unscientific basis of acupuncture had been addressed, only that it might have achieved a placebo response. Is Dr. Gelfand suggesting that would be sufficient, although there are some problems in the trial. What if that became the standard for recommending medications and medical procedures?
With increasing success in getting acupuncture and other now-called “integrative medicine” approaches ensconced in cancer centers and reimbursed by insurance, will be facing again and again some of the issues that started this blog post. Is acupuncture not doing obvious from a reason for reimbursing it? Trials like this one can be cited in support for reimbursement.
The JAMA: Internal Medicine report of an RCT of acupuncture for preventing migraines
Participants were randomly assigned to one of three groups: true acupuncture, sham acupuncture, or a waiting-list control group.
Participants in the true acupuncture and sham acupuncture groups received treatment 5 days per week for 4 weeks for a total of 20 sessions.
Participants in the waiting-list group did not receive acupuncture but were informed that 20 sessions of acupuncture would be provided free of charge at the end of the trial.
As the editorial comment noted, this is incredibly intensive treatment that burdens patients coming in five days a week for treatment for four weeks. Yet the effects were quite modest in terms of number of migraine attacks, even if statistically significant:
The mean (SD) change in frequency of migraine attacks differed significantly among the 3 groups at 16 weeks after randomization (P < .001); the mean (SD) frequency of attacks decreased in the true acupuncture group by 3.2 (2.1), in the sham acupuncture group by 2.1 (2.5), and the waiting-list group by 1.4 (2.5); a greater reduction was observed in the true acupuncture than in the sham acupuncture group (difference of 1.1 attacks; 95%CI, 0.4-1.9; P = .002) and in the true acupuncture vs waiting-list group (difference of 1.8 attacks; 95%CI, 1.1-2.5; P < .001). Sham acupuncture was not statistically different from the waiting-list group (difference of 0.7 attacks; 95%CI, −0.1 to 1.4; P = .07).
There were no group by time differences in use of medication for migraine. Receiving “true” versus sham acupuncture did not matter.
Four acupoints were used per treatment. All patients received acupuncture on 2 obligatory points, including GB20 and GB8. The 2 other points were chosen according to the syndrome differentiation of meridians in the headache region. The potential acupoints included SJ5, GB34, BL60, SI3, LI4, ST44, LR3, and GB40.20. The use of additional acupoints other than the prescribed ones was not allowed.We chose the prescriptions as a result of a systematic review of ancient and modern literature,22,23 consensus meetings with clinical experts, and experience from our previous study.
Note that the “headache region” is not the region of the head where headaches occur, the selection of which there is no scientific basis. Since when does such a stir fry of ancient and contemporary wisdom, consensus meetings with experts, and the clinical experience of the investigators become the basis of the mechanism justified for study in a clinical trial published in a prestigious American medical journal?
What was sham about the sham acupuncture (SA) treatment?
The number of needles, electric stimulation, and duration of treatment in the SA group were identical in the TA group except that an attempt was not made to induce the Deqi sensation. Four nonpoints were chosen according to our previous studies.
From the trial protocol, we learn that the effort to induce the Deqi sensation involves the acupuncturist twirling and rotating the needles.
In a manner that can easily escape notice, the authors indicate that they acupuncture was administered by electro stimulation.
In the methods section, they abruptly state:
Electrostimulation generates an analgesic effect, as manual acupuncture does.21
I wonder if the reviewers or the editorialist checked this reference. It is to an article that provides the insight that “meridians” -the 365 designated acupuncture points- are identified on a particular patient by
feeling for 12 organ-specific pulses located on the wrists and with cosmological interpretations including a representation of five elements: wood, water, metal, earth, and fire.
The authors further state that they undertook a program of research to counter the perception in the United States in the 1970s that acupuncture was quackery and even “Oriental hypnosis.” Their article describes some of the experiments they conducted, including one in which the benefits of a rabbit having received finger-pressure acupuncture was transferred to another via a transfusion of cerebrospinal fluid.
In discussing the results of the present study in JAMA Internal Medicine, the authors again comment in passing:
We added electrostimulation to manual acupuncture because manual acupuncture requires more time until it reaches a similar analgesic effect as electrical stimulation.27 Previous studies have reported that electrostimulation is better than manual acupuncture in relieving pain27-30 and could induce a longer lasting effect.28
The citations are to methodologically poor laboratory studies in which dramatic results are often obtained with very small cell size (n= 10).
Can we dispense with the myth that the acupuncture provided in this study is an extension of traditional Chinese needle therapy?
It is high time that we dispense with the notion that acupuncture applied to migraines and other ailments represents a traditional Chinese medicine that is therefore not subject to any effort to critique its plausibility and status as a science-based treatment. If we dispense with that idea, we still have to confront how unscientific and nonsensical the rationale is for the highly ritualized treatment provided in this study.
An excellent article by Ben Kavoussi offers a carefully documented debunking of:
reformed and “sanitized” acupuncture and the makeshift theoretical framework of Maoist China that have flourished in the West as “Traditional,” “Chinese,” “Oriental,” and most recently as “Asian” medicine.
Kavoussi, who studied to become an acupuncturist, notes that:
Traditional theories for selecting points and means of stimulation are not based on an empirical rationale, but on ancient cosmology, astrology and mythology. These theories significantly resemble those that underlined European and Islamic astrological medicine and bloodletting in the Middle-Ages. In addition, the alleged predominance of acupuncture amongst the scholarly medical traditions of China is not supported by evidence, given that for most of China’s long medical history, needling, bloodletting and cautery were largely practiced by itinerant and illiterate folk-healers, and frowned upon by the learned physicians who favored the use of pharmacopoeia.
In the early 1930s a Chinese pediatrician by the name of Cheng Dan’an (承淡安, 1899-1957) proposed that needling therapy should be resurrected because its actions could potentially be explained by neurology. He therefore repositioned the points towards nerve pathways and away from blood vessels-where they were previously used for bloodletting. His reform also included replacing coarse needles with the filiform ones in use today.38 Reformed acupuncture gained further interest through the revolutionary committees in the People’s Republic of China in the 1950s and 1960s along with a careful selection of other traditional, folkloric and empirical modalities that were added to scientific medicine to create a makeshift medical system that could meet the dire public health and political needs of Maoist China while fitting the principles of Marxist dialectics. In deconstructing the events of that period, Kim Taylor in her remarkable book on Chinese medicine in early communist China, explains that this makeshift system has achieved the scale of promotion it did because it fitted in, sometimes in an almost accidental fashion, with the ideals of the Communist Revolution. As a result, by the 1960s acupuncture had passed from a marginal practice to an essential and high-profile part of the national health-care system under the Chinese Communist Party, who, as Kim Taylor argues, had laid the foundation for the institutionalized and standardized format of modern Chinese medicine and acupuncture found in China and abroad today.39 This modern construct was also a part of the training of the “barefoot doctors,” meaning peasants with an intensive three- to six-month medical and paramedical training, who worked in rural areas during the nationwide healthcare disarray of the Cultural Revolution era.40 They provided basic health care, immunizations, birth control and health education, and organized sanitation campaigns. Chairman Mao believed, however, that ancient natural philosophies that underlined these therapies represented a spontaneous and naive dialectical worldview based on social and historical conditions of their time and should be replaced by modern science.41 It is also reported that he did not use acupuncture and Chinese medicine for his own ailments.42
What is a suitable comparison/control group for a theatrical administration of a placebo?
A randomized double-blind crossover pilot study published in NEJM highlight some of the problems arising from poorly chosen control groups. The study compared an inhaled albuterol bronchodilator to one of three control conditions placebo inhaler, sham acupuncture, or no intervention. Subjective self-report measures of perceived improvement in asthma symptoms and perceived credibility of the treatments revealed only that the no-intervention condition was inferior to the active treatment of inhaled albuterol and the two placebo conditions, but no difference was found between the active treatment and the placebo conditions. However, strong differences were found between the active treatment in the three comparison/control conditions in an objective measure of physiological responses – improvement in forced expiratory volume (FEV1), measured with spirometry.
One take away lesson is we should be careful about accepting subjective self-report measures when objective measures are available. One objective measure in the present study was the taking of medication for migraines and there were no differences between groups. This point is missed in both the target article in JAMA Internal Medicine and the accompanying editorial.
The editorial does comment on the acupuncturists being unblinded – they clearly knew when they are providing the preferred “true” acupuncture and when they were providing sham. They had some instructions to avoid creating a desqi sensation in the sham group, but some latitude in working till it was achieved in the “true” group. Unblinded treatment providers are always a serious risk of bias in clinical trials, but we here we have a trial where the primary outcomes are subjective, the scientific status of desqi is dubious, and the providers might be seen as highly motivated to promote the “true” treatment.
I’m not sure why the editorialist was not stopped in her tracks by the unblinded acupuncturists – or for that matter why the journal published this article. But let’s ponder a bit difficulties in coming up with a suitable comparison/control group for what is – until proven otherwise – a theatrical and highly ritualized placebo. If a treatment has no scientifically valid crucial ingredient, how we construct a comparison/control group differs only in the absence of the active ingredient, but is otherwise equivalent?
There is a long history of futile efforts to apply sham acupuncture, defined by what practitioners consider the inappropriate meridians. An accumulation of failures to distinguish such sham from “true” acupuncture in clinical trials has led to arguments that the distinction may not be valid: the efficacy of acupuncture may depend only on the procedure, not choice of a correct meridian. There are other studies would seem to show some advantage to the active or “true” treatments. These are generally clinical trials with high risk of bias, especially the inability to blind practitioners as to what she treatment they are providing.
There are been some clever efforts to develop sham acupuncture techniques that can fool even experienced practitioners. A recent PLOS One article tested needles that collapsed into themselves.
Up to 68% of patients and 83% of acupuncturists correctly identified the treatment, but for patients the distribution was not far from 50/50. Also, there was a significant interaction between actual or perceived treatment and the experience of de qi (p = 0.027), suggesting that the experience of de qi and possible non-verbal clues contributed to correct identification of the treatment. Yet, of the patients who perceived the treatment as active or placebo, 50% and 23%, respectively, reported de qi. Patients’ acute pain levels did not influence the perceived treatment. In conclusion, acupuncture treatment was not fully double-blinded which is similar to observations in pharmacological studies. Still, the non-penetrating needle is the only needle that allows some degree of practitioner blinding. The study raises questions about alternatives to double-blind randomized clinical trials in the assessment of acupuncture treatment.
This PLOS One study is supplemented by a recent review in PLOS One, Placebo Devices as Effective Control Methods in Acupuncture Clinical Trials:
Thirty-six studies were included for qualitative analysis while 14 were in the meta-analysis. The meta-analysis does not support the notion of either the Streitberger or the Park Device being inert control interventions while none of the studies involving the Takakura Device was included in the meta-analysis. Sixteen studies reported the occurrence of adverse events, with no significant difference between verum and placebo acupuncture. Author-reported blinding credibility showed that participant blinding was successful in most cases; however, when blinding index was calculated, only one study, which utilised the Park Device, seemed to have an ideal blinding scenario. Although the blinding index could not be calculated for the Takakura Device, it was the only device reported to enable practitioner blinding. There are limitations with each of the placebo devices and more rigorous studies are needed to further evaluate their effects and blinding credibility.
Really, must we we await better technology the more successfully fool’s acupuncturists and their patients whether they are actually penetrating the skin?
Results of the present study in JAMA: Internal Medicine are seemingly contradicted by the results of a large German trial that found:
Results Between baseline and weeks 9 to 12, the mean (SD) number of days with headache of moderate or severe intensity decreased by 2.2 (2.7) days from a baseline of 5.2 (2.5) days in the acupuncture group compared with a decrease to 2.2 (2.7) days from a baseline of 5.0 (2.4) days in the sham acupuncture group, and by 0.8 (2.0) days from a baseline if 5.4 (3.0) days in the waiting list group. No difference was detected between the acupuncture and the sham acupuncture groups (0.0 days, 95% confidence interval, −0.7 to 0.7 days; P = .96) while there was a difference between the acupuncture group compared with the waiting list group (1.4 days; 95% confidence interval; 0.8-2.1 days; P<.001). The proportion of responders (reduction in headache days by at least 50%) was 51% in the acupuncture group, 53% in the sham acupuncture group, and 15% in the waiting list group.
Conclusion Acupuncture was no more effective than sham acupuncture in reducing migraine headaches although both interventions were more effective than a waiting list control.
I welcome someone with more time on their hands to compare and contrast the results of these two studies and decide which one has more credibility.
Maybe we step should back and ask “why is anyone care about such questions, when there is such doubt that a plausible scientific mechanism is in play?”
Time for JAMA: Internal Medicine to come clean
The JAMA: Internal Medicine article on acupuncture for prophylaxis of migraines is yet another example of a publication where revelation of earlier drafts, reviewer critiques, and author responses would be enlightening. Just what standard to which the authors are being held? What issues were raised in the review process? Beyond resolving crucial limitations like blinding of acupuncturists, under what conditions would be journal conclude that studies of acupuncture in general are sufficiently scientifically unsound and medically irrelevant to warrant publication in a prestigious JAMA journal.
Alternatively, is the journal willing to go on record that it is sufficient to establish that patients are satisfied with a pain treatment in terms of self-reported subjective experiences? Could we then simply close the issue of whether there is a plausible scientific mechanism involved where the existence of one can be seriously doubted? If so, why stop with evaluations with subjective pain would days without pain as the primary outcome?
We must question the wisdom of JAMA: Internal Medicine of inviting Dr. Amy Gelfand for editorial comment. She is apparently willing to allow that demonstration of a placebo response is sufficient for acceptance as a clinician. She also is attached to the University of California, San Francisco Headache Center which offers “alternative medicine, such as acupuncture, herbs, massage and meditation for treating headaches.” Endorsement of acupuncture in a prestigious journal as effective becomes part of the evidence considered for its reimbursement. I think there are enough editorial commentators out there without such conflicts of interest.
I will soon be offering scientific writing courses on the web as I have been doing face-to-face for almost a decade. Sign up at my new website to get notified about these courses, as well as upcoming blog posts at this and other blog sites. Get advance notice of forthcoming e-books and web courses. Lots to see at CoyneoftheRealm.com.