I used to be of the opinion that there might just be something to acupuncture. No, I never thought there was anything to the notion that acupuncture “works” by somehow rerouting the flow of a magical life force (qi) that no scientific instrument can detect and that no practitioner of acupuncture (or other practioners “healing arts” that invoke qi or something like it as the reason that they can heal) can detect either, even as they claim to “release blockages” of or somehow improve its flow. Rather, I wondered whether the simple act of sticking needles into the skin might release some hormone, endorphins, or other active physiological messnger that accounted for the rather modest effects attributed to acupuncture. Another possible explanation for its apparent efficacy was that it was a form of counterirritant that caused pain to be sensed as less intense. Either way, I didn’t consider it totally implausible that acupuncture might do something therapeutic through one or more of the good, old-fashioned physiologic mechanisms that I was taught in medical school.
That was then.
Over the last several months, however, I’ve been becoming more and more skeptical of acupuncture. Perhaps it’s because I had rarely looked at the actual peer-reviewed medical literature about acupuncture before, while over the last few months I’ve delved more and more into it. As I did so, the the realization dawned on me just how bad most of the studies hyped as “proof” that acupuncture “works” are. I’ve even blogged about a couple of studies that either failed to show any effect of acupuncture greater than placebo, had serious flaws that invalidated the claims of the investigators, or showed that perception among patients of efficacy was not reality. Meanwhile, über-skeptic Steve Novella also schooled me a bit in why most studies of acupuncture are poorly designed and hyped by the press as “proving” that acupuncture “works” when the study shows nothing of the sort and how many studies of “acupuncture” are actually a case of misdirection in which electrical current is passed through the needles, making them in essence clinical trials of the efficacy trancutaneous electrical nerve stimulators (TENS), a perfectly acceptable “conventional” therapy for pain for which there is abundant evidence for efficacy.
Recently, a study on the efficacy of acupuncture for treating hot flashes in breast cancer patients was published in a high profile journal by investigators at one of the premiere cancer centers in the U.S., if not the world. What? You didn’t hear about it? Neither did I, until I actually happened to be perusing the stack of my most recent journals. I wonder why it wasn’t publicized.
This new study1 now tells me that acupuncture appears to be useless for hot flashes in breast cancer patients undergoing hormonal or chemotherapy. The study comes out of the Integrative Medicine Service at cancer powerhouse Memorial Sloan-Kettering Cancer Center (another one to add to my Academic Woo Aggregator, perhaps?) and was recently published in the Journal of Clinical Oncology, and its senior author was Barry Cassileth, the author of The Alternative Medicine Handbook: The Complete Reference Guide to Alternative and Complementary Therapies. I looked around for breathless news stories hyping this study. Oddly enough, I didn’t find any, not even a press release on Eurekalert!. The reason was, I’m sure, that this was a negative study.
Apparently the mainstream media suffers from the problem of publication bias too.
Before I discuss the study itself, I wondered why one would hypothesize that acupuncture would be useful for hot flashes. Certainly, this is a problem that interferes with the quality of life of premenopausal women who undergo cancer therapy, sometimes so seriously that the occasional woman even decides that she would rather take the increased risk of recurrence of their cancer than put up with the symptoms. For some, the chemotherapy itself can put them into temporary menopause; while for many others it is the treatment with estrogen-blocking drugs like tamoxifen that induces a state of menopause for as long as the patient is taking the drug, which is usually for five years after their initial breast cancer therapy. Because of the increased risk of breast cancer, particularly in a breast cancer survivor, using estrogen replacement to alleviate menopausal symptoms is not usually a good option. Worse, various non-estrogen treatments, including herbal remedies, have in general not produced convincing evidence of efficacy, although Vitamin E appears to be able to produce a mild decrease in the number of hot flashes.
This is where plausibility comes into the picture. Acupuncture is proclaimed as a treatment for many medical conditions that are unrelated, with no common physiological mechanism to explain why sticking needles in the skin in specified ways would alleviate the symptoms of such a diverse group of clinical entities. In other words, unlike the claims of “individualized treatments,” that purveyors of alternative medicine so like to make, in the world of acupuncture, it’s one size fits all for the most part, the only leeway being how many needles are put in and where–all without a plausible scientific basis to suggest why any needles would do any good. Such is the case with acupuncture and menopausal symptoms. None of this, of course, keeps true believers from trying to apply acupuncture to virtually every condition known to man.
Be that as it may, this study, however shaky the the scientific basis under which it was done (and apparently done pretty well) appears to have been funded by the National Center for Complementary and Alternative Medicine. Moreover, it was carried out at one of the top two cancer centers in the U.S., an old and respected institution. The study design was a randomized, controlled subject-blinded trial. The primary endpoint was the number of hot flashes reported by patients per day. The meridians chosen were du mai, gallbladder, bladder, pericardium, heart, kidney stomach, and spleen at specific acupuncture points. How the acupuncturists chose these points, don’t ask me. It isn’t explained in the paper. What is explained in the paper is that this set of acupuncture points was different from the ones used in a pilot study:
When the study was initially started, 27 participants were accrued and were treated with a set of points different than those shown in Figure 1. At this point, there was a change in staffing. The new group of acupuncturists believed that a different set of points (Table 1) would be more appropriate. We prespecified that we would accrue sufficient patients on the new point prescription to meet the original sample size requirements and that our primary analysis would include only patients on the new point prescription. Seventy-two participants were accrued to this new regimen. Data presented here derived solely from those 72 participants.
Again, who knows how this was determined? However, the sample size and power calculations appear to be adequate, and the investigators did appear to accrue a large enough number of patients. I also note right here that the way in which the subjects were blinded was almost, but not quite, the optimal way:
In the true acupuncture group, the needles used were stainless-steel filiform, needles sized 0.20 x 30 mm and manufactured by Seirin Corp (Shizuoka, Japan). After sterile swabbing of the skin, needles were inserted 0.25 to 0.5 inches into the skin at the designated acupuncture points and were manipulated manually to obtain De Qi.31 No electrical stimulation or other interventions were applied.
In the sham acupuncture group, Streitberger sham needles sized 0.30 x 30 mm and manufactuered by Asiamed (Pullach, Germany)37 were applied a few centimeters away from the points listed in Table 1. Rather than penetrating the skin, the needle retracted inside its handle after insertion through an adhesive tape placed on a plastic supporting ring. This type of sham needle has been shown to have high participant credibility and has been successfully implemented in randomized, controlled trials.38 The frequency and duration of the sham acupuncture intervention were identical to those of true acupuncture. To ensure consistency in technique, the therapists were coached by a single acupuncturist who also observed treatments periodically for integrity. Participants randomly assigned to the control group were offered eight sessions of true acupuncture starting at week 7. To aid the blinding process, all patients were asked to relax on the treatment table, gentle music was played, and an eye pillow was offered. In both groups, needles were retained for 20 minutes and then were removed. Participants with lymphedema were not administered needles in the affected arm.
Although the best “placebo acupuncture” needles were used, this design leaves something to be desired. For one thing, the practitioners were not blinded, as they are in the best designs and as is possible using these retractable needles. For another, I can’t figure out why for the “sham” acupuncture the investigators both used the retractable needles to stick the sham acupuncture points. What should have been done was to use the “true” acupuncture needles at the “sham” acupuncture points and to add an additional experimental group with in which the “sham” needles were used for the “true” acupuncture points. That, and blind the acupuncturists to the treatment group, at least for the patients in the groups getting either the “true” acupuncture of the “sham” needles in the “true” acupuncture points. That’s what needs to be done if one really wants to test properly whether acupuncture “works,” or not. Still, the design of this study was better than most acupuncture studies:
Note the crossover design. Such a feature of a clinical trial is usually placed there to see if switching patients from the placebo arm to the treatment arm results in an effect. Finally, the study relied on self-reporting of hot flashes. As an accompanying editorial states, this was somewhat odd, given that there has been a reliable objective means of measuring hot flashes for a long time, and most investigators now believe that both patient reporting and objective measurement should be used in the best designed trials. Be that as it may, the results of this study were–shall we say?–underwhelming. The mean number of hot flashes per day was reduced from 8.7 to 6.2 in the “true” acupuncture group and from 10.0 to 7.6 in the sham group, both with wide variability. “True” acupuncture was associated with 0.8 fewer hot flashes per day than sham at 6 weeks, but the difference did not even come close to statistical significance. When participants in the sham acupuncture group were crossed over to true acupuncture, a further reduction in the frequency of hot flashes was supposedly seen, but again this was not even close to statistically significant. The reduction in hot flash frequency was reported to have persisted for up to 6 months after the completion of treatment. In all cases, the confidence intervals for the difference in the number of hot flashes in the sham and “true” acupuncture groups encompassed zero. Given that there was a reduction of hot flashes in both the sham and “true” acupuncture groups, the most likely explanation for the results of this study is the placebo effect. Maybe we should just treat women with soothing music, dark rooms, and eye pillows.
Of course, the authors try to salvage something out of a resoundingly negative trial using a most unconvincing argument:
There are several possible explanations of our findings in light of the above previous studies. First, it may be that the interventions used as sham controls were not entirely inactive….
Second, symptom improvement may result from the natural course of symptoms or from the psychological impact of treatment. In drug trials with a placebo control, the placebo effect on hot flashes frequency can vary from 13% to 22%. Improvement in our sham acupuncture group (24%) is close to that range. All trials of symptoms in which a certain baseline symptom severity is an eligibility criterion will be subject to regression to the mean. It is also widely believed that psychological impact of receiving treatment–the time and attention from a practitioner, and the patient’s belief that they will be helped–is of therapeutic value. Both true and sham acupuncture also may create a relaxation effect, which can reduce hot flashes…
The third possible explanation for our findings is that the acupuncture intervention may not have been optimal. This may be because the point prescription was inadequate. Most investigators select acupuncture points based on classical theory, previous research reports, and/or expert opinion. This is an inherent limitation of all acupuncture research, because there is no reliable and consistent way to determine what would constitute the ideal prescription.
If there is no reliable and consistent way to determine the ideal “prescription” of acupuncture, how, then, do acupuncturists figure out how to treat a given patient? Doesn’t this last line alone send up huge red flags that the acupuncture emperor has no clothes?
Finally, the authors can’t resist stating that they “can’t rule out” the possibility that a longer course of acupuncture would have resulted in a statistically significant difference in the number of hot flashes in the trial subjects receiving “true” acupuncture. I suppose that’s possible, but the patients received four weeks of acupuncture therapy. There has to come a point when enough is enough. Longer treatment would also make regression to the mean more of a concern that has to be controlled for. Finally, there is the question of whether the effects of acupuncture would be clinically useful even if the study did show a statistically significant decrease in hot flashes. As pointed out in the accompanying editorial, the reduction in hot flash frequency was to only around 20% below baseline at the start of the study for both the sham and “true” acupuncture groups. This is far below the 50% or greater reduction in hot flashes desired by most women suffering from them. In other words, even if acupuncture “worked,” it would probably be clinically irrelevant.
In the end, this is a negative study, no matter how much its authors may try to spin it as anything other or speculate that acupuncture might have worked if they had continued the treatment longer. It’s also the reason why you probably haven’t heard about it, as you can bet that a major study like this from a research powerhouse like Memorial Sloan-Kettering Cancer Center published in a very widely read, high impact journal like the Journal of Clinical Oncology would have been trumpeted to every news outlet in the land if it had shown a statistically significant decrease in hot flashes in women in the “true” acupuncture group. It didn’t; so it wasn’t.
In any case, the speculation about whether a longer course of acupuncture would have yielded statistically significant results will, I predict, provide the investigators with a rationale to try to get more money from NCCAM for a followup study. It’s your tax dollars hard at work.