Much have been made in the media recently, of a February 2013 paper, published by a German group in the Annals of Internal Medicine, claiming that acupuncture may help relieve seasonal allergies. Always interested in examining the bold claims of efficacy by various forms of pseudoscientific, wannabe-medicine modalities (such as homeopathy, naturopathy, and so forth), I elected to go to the source; the paper was behind an annoying paywall, but thankfully, I had institutional access, and dove in.
The paper describes a randomized, controlled, multicenter clinical trial of acupuncture in patients suffering from allergic rhinitis associated with the season. Rhinitis is the inflamed condition of the inner nasal passageway, leading to stuffy or runny nose, irritation of the nasal passage and back of throat which induces sneezing and coughing. Rhinitis may be secondary to an allergic response (hence “allergic rhinitis”) that people may have to airborne dander or dust, tree or grass pollen, or other allergens, during particular seasons.
Individuals sensitized to these allergens produce certain antibodies to them, called IgE, which in turn binds to special types of immune cells, called Mast cells and Basophils. This leads to release of a substance called histamine, a potent mediator of inflammation and allergic responses. Apart from nasal congestion, eye, ear and throat symptoms are common.
In Western societies, about 10-25% people, many of them children, face the annual occurrence of allergic rhinitis. Ordinarily, the treatments for this condition have long been pretty standardized, geared towards prevention or reduction of symptoms. Pharmacological interventions, in form of steroids and anti-histamine agents, are highly effective – even over-the-counter ones; in extreme cases, desensitization via prolonged immunotherapy may be prescribed, which suppresses IgE formation in the body.
The bottom-line is, the existing therapies work, and people get better, with symptomatic relief. And yet…
… yet, as the authors of the study have noted in the paper, many people seek out unproven, unscientific alternative medicine modalities looking for relief from symptoms. About 1 out of 5 of these patients feel acupuncture is going to help them, regardless of the fact that evidence for actual efficacy or benefit of acupuncture in allergic rhinitis is severely lacking. Score 1 for gullibility.
Taking cognizance of the fact that some people still choose acupuncture for allergic rhinitis, the authors designed a clinical trial to assess the efficacy of this intervention upon two variables, disease-specific quality of life (in other words, whether the patients feel they’re getting better), and secondly, the actual need for anti-histamine medication (indicative of the patients’ physiological condition). They decided to study the effects of acupuncture along with an antihistaminic, cetirizine, to be used as a rescue medication (one that provides a quick relief when needed); their comparators were sham acupuncture (in which so-called ‘real’ acupuncture therapy, using ‘meridians’ and points prescribed by Traditional Chinese Medicine, wouldn’t be applied, but needles would be applied randomly) along with cetirizine, and cetirizine alone.
This is a nice design for a controlled trial. However, when applied to Tooth Fairy science, there is a significant problem.
Coined by Harriet Hall, MD, accomplished physician and blogger, Tooth Fairy science refers to a research undertaking on a hypothesis before establishing that the hypothesis is plausible in reality, and/or the phenomenon under study actually occurs/exists. I shall leave you to follow the above link for the definition, but acupuncture is one such phenomenon – its efficacy is one such hypothesis, which has so long never been unequivocally proved empirically, except, perhaps, in the imagination of TrueBelievers™. This is why clinical trials with an unproven modality like acupuncture can never be designed for a head-to-head comparison with existing medical therapies, because of moral and ethical considerations, and obligations of conscientious physicians towards their patients. In this study, all patients took doses of cetirizine. Therefore, the assessment of the outcome would necessarily depend upon the rigorousness of observations and prodigious statistical legerdemain.
422 patients were randomly assigned to the treatment groups (212, acupuncture; 102, sham acupuncture; 108, cetirizine; the actual analysis was done with slightly less number of patients for various reasons, mentioned in figure 2). These were late 20s to late 30s folks, predominantly women, and mostly from Berlin/Brandenburg and Bavaria, all having suffered seasonal allergy-associated rhinitis in the previous year – but mostly (3 out of every 5) of a shorter duration.
There were variations in the acupuncture procedure performed on patients – number of needles used, time of needle retention. Someone who is more versed with these variations can perhaps comment on the possible effects of these variations on the outcome.
Throughout the study, patients, as well as non-physician personnel, were blinded to the treatment assignment, which means that the patients didn’t know to begin with what kind of treatment they would receive. However, an important point to be noted is that – as mentioned – about 80% of participants came to take part after reading newspaper articles – placed by the study recruiters – about the use of acupuncture for allergic rhinitis. It is not unlikely that these patients were already favorably inclined towards accessing acupuncture for their treatment, a possible real source of bias. This is particularly significant if one considers that, by the study design, RM (Rescue Medicine) Scores and part of RQLQ (Rhinitis Quality of Life Questionnaire) were assessed by self-reported symptom diaries and answers to questionnaires. The mind boggles at the implication.
The remaining 20% were recruited by physicians at trial centers. It would, therefore, have been interesting to see the total study outcome stratified according to mode of recruitment also.
It is perhaps a reflexion of this fact, that at the time of recruitment, 4 out of every 5 patients started with a high expectation of acupuncture efficacy; in addition, about 20% of them had previous exposure to acupuncture. These are the same folks who ended up finding themselves in the acupuncture group in most numbers (1 in 4 patients in this group had prior acupuncture). This makes me worried about the quality of blinding of the study. According to the authors,
… recipients of real acupuncture rated the question, “How confident do you feel that acupuncture can alleviate your complaint?,” higher than did recipients of sham acupuncture (P = 0.016).
This is a statistically significant difference. Since belief in acupuncture was equivalent at the onset of treatment, if the patients were indeed blinded to the intervention, why would the sham group show a lower confidence in acupuncture than those in the real group? The authors don’t explain this further, beyond mentioning a possible unblinding en passim in the discussion, and indicating that “… effects of acupuncture compared with RM in this study might have been affected by patient beliefs about acupuncture.“
In the results, the authors have stated that the RQLQ and RM Scores decreased more in the acupuncture group than in the controls. However, in the longer term (end of fourth month and in the second year), scores in all the groups pretty much even out. In the cetirizine group, these later observations are, of course, confounded by the inexplicable study design of giving acupuncture sessions to cetirizine-taking patients. It was almost as if the study designers were determined to show an effect of acupuncture anywhichway.
It also doesn’t explain why all the scores seem to return to the baseline or higher in the second year, per figure 3.
Image ©The American College of Physicians; Figure adapted from Brinkhaus et al., Ann Intern Med. 2013;158(4):225-234.
The problem with any of such subjective scoring system is always the assessment of the biological/clinical significance, particularly in absence of mechanistic explanations. What does a decrease of 0.3, 1.5 or 2 points mean in absolute or relative terms? In microbiology, for example, any drug or intervention that reduces the number of bacteria by 3 logs (≥1000-fold) is considered clinically significant. What do these scores mean in terms of actual effect on the physiology of the patient? How does acupuncture address the primary cause of the symptoms of allergic rhinitis, the local inflammatory response and the inflammatory mediators running amok?
Such is the nature of Tooth Fairy science.
To their credit, the authors do comment in the discussion somewhat on this.
…CIs surrounding the estimates of improvement included values that were less than predefined thresholds for clinically important differences, so the clinical significance of the findings is uncertain. There were no between-group differences in responses at 16 weeks, and acupuncture led to greater improvements than sham acupuncture (but not RM) after the 8-week follow-up phase in the second year, with CIs that again included differences of uncertain clinical significance. [All emphases, mine]
In the discussion, the authors mention a few studies, mostly from one group (one of which, Dr. Pfab, is a co-author in this paper) and a review, which have attempted mechanistic explanations for the effects of acupuncture. However, the mechanisms that these papers have expounded on relate to itch, which until recently was thought to be related to pain receptors (but may actually involve a distinct neural circuit altogether). The pathways are not the same as those used by allergic rhinitis, and unlike the latter, antihistamines don’t work on most forms of itch.
So, no… Still no mechanism for the hypothesized beneficial action of acupuncture on allergic rhinitis. But that does not prevent the author from claiming benefit as such. Score 1 for pseudoscience.
Now the headlines
My attention to this study was drawn yesterday via the Twitter feed of an Indian TV News channel, Zee News; aware of the influence of several pseudoscientific modalities in Indian healthcare, I thought, perhaps in a newfound spirit of regional co-operation, India was embracing TCM as well; the more, the merrier. I was wrong. Zee News, or more precisely, its “Health” News (scarequotes are fully intended) section, was merely reporting on the German study, quoting Fox News.
In order to gauge the Media response, I decided to engage in a Google Search with the study citation as a search term. Not unexpectedly, the media headlines turning in the search were almost all uncritical statements designed to highlight an impression of benefit, and the actual reports therein were accordingly vacuous. Here is a sample of my search results, aggregated from first 3 pages:
There was a single notable exception, Medscape Medical News – much plaudits to them for the appropriately critical assessment. The question is: can this poor quality of general headlining and reporting be explained away by the much-discussed difference between scientific report and journalism?
Comprehensive analysis here, as always! However, my opinion is that even if acupuncture has no physiological merit, if it does have a placebo effect that’s soothing, then fine. At the end of the day, the patient feels better, isn’t that the point?
Thank you for the kind comment, Khalil. What you say about the therapy is rapidly becoming the norm in today’s emphasis on “patient centric medicine”. If the patient “feels better” then why not? On a superficial level it does appear that way, doesn’t it? That, even if the therapy’s ineffective, if the patient feels better, then what’s the harm?
Well, the harm of pseudoscience is manifold, and it applies to acupuncture as well.
You see, “feel better” can’t be quantified, and there is no guarantee that all patients would feel that way. It is, as I said, unethical to project that, by this treatment, they will.
Great work, Kausik. I wonder at medical/scientific journals adopting the policy of publishing results so reliant on such subjective criteria. If (though it is unclear to me) the authors were, at the outset, attempting to ‘test’ for improved quality of life, then recruiting so many ‘acupuncture-inclined’ subjects means it couldn’t fail. Which provides a ‘disprovable’ argument for advocates of an unproven treatment.
‘Since belief in acupuncture was equivalent at the onset of treatment, if the patients were indeed blinded to the intervention, why would the sham group show a lower confidence in acupuncture than those in the real group?’
I’ve read about sham needles; but sham site-application of those needles seems to me more problematic: wouldn’t ‘acupuncture-inclined’ subjects be more likely to cotton on that application was random and not ‘meridian’-sited?
I note there is an online comment facility at the journal…
‘… can this poor quality of general headlining and reporting be explained away by the much-discussed difference between scientific report and journalism?’
Well, perhaps by the difference between scientific report and irresponsible journalism. (But is this example really ‘scientific’?)
In response to Khalil – I think we have to be very careful when we attempt to distinguish between apologetic defence of nice CAM people who limit themselves to genuine effort to alleviate mild health conditions (and so induce a placebo-style feel better improvement); and the charlatan brand that sells ‘cure’ for serious conditions. I’m not at all sure there is a safe demarcation here, and ethics – being honest with patients as to the efficacy or otherwise of whatever treatment – should override.
Edzard Ernst has had more to say recently on acupuncture:
http://edzardernst.com/2013/05/acupuncture-if-it-looks-like-a-placebo-feels-like-a-placebo-behaves-like-a-placebo-perhaps-it-is-a-placebo/
http://edzardernst.com/2013/06/acupuncture-a-needle-in-the-haystack-or-a-theatrical-placebo/
As usual, you make some great points, Lee. Also, thanks for the links to Prof. Ernst’s essays. They are educational.
Kausik, I think you may find this of interest:
http://www.nightingale-collaboration.org/news/150-getting-the-point.html
Fascinating analysis, I’m a complete sceptic of such nonsense. However, I have always regarded it as fairly harmless, and indeed, a placebo. I cannot, however, forgive the use of homeopathy on humans, let alone animals – many vets practice this cruel and antiquated pseudo medicine on animals which obviously have no say in the matter. The perpetuation by the media that such archaic practices are acceptable is disgraceful.
I think you have forgotten that some patients favor alternative medicine and want a holistic approach to healing.
Or the fact, that many patients who decide to try acupuncture have exhausted other methods and never felt better.
Jerry, I see that you offer chiropractic and acupuncture to patients. Therefore, I am not surprised at your comments. Vulnerable and ill patients often do not know any better and will often grasp at straws with the desire to be cured of their chronic, debilitating disorders. The “holistic approach to healing” – so favorite of AltMed aficionados – is merely a mishmash of catchy buzzphrases with a healthy dollop of eastern mysticism and no basis in reality. To this, too, yes, patients will sometimes turn in their desperation.
Conventional medicine, despite its best efforts, may not always be able to alleviate or ameliorate the conditions that these patients present with, but conventional medicine will neither lie to the patients, nor stop trying – methodically, meticulously – to figure out the disease mechanisms, and thereby, an appropriate therapy targeting the disease.
Alternative ‘medicine’ (such as the ones you offer), on the other hand, will continue to take undue advantage of the vulnerabilities of these poor patients, relying on – (a) claims of credit for various self-mitigating conditions that many of these patients often have in part, and more egregiously, (b) subtle psychological manipulation of these patients through outright lies and/or disinformation in absence of empirical evidence, and indeed, any scientific basis.
Perhaps you sincerely think you are helping these patients. But at some point, you may want to take a step back and think about the ethics of misleading vulnerable patients and causing greater harm in the long run.
In any case, I note that your comment has nothing to do with the content of my post.
Isn’t it odd how people who propose that a cricked back, imbalance of qi or some other such nonsense is the “one true cause” of disease, always pretend to be holistic?
My doctor is holistic. He focuses n the whole patient, and he can use or call upon the full spectrum of diagnostic and therapeutic techniques. How often to chiropractors refer patients to real surgeons and doctors? Not only that, my doctor’s aim is a cured patient. He’s happy when people are not ill and not coming to the office. He’s happy if he only sees me at rugger matches!
As far as I can tell main aim of quacks and charlatans is to keep people coming back for as long as possible, I’ve never heard of a chiropractor discharging a cured patient!
So why does excessive focus on a delusional belief qualify as “holistic” in a way that real doctoring doesn’t?
Great question, Guy. Destined to be one of those eternal mysteries, I guess.