MD, PhD, FMedSci, FSB, FRCP, FRCPEd

clinical trial

This week is acupuncture awareness week, and I will use this occasion to continue focusing on this therapy. This first time ever event is supported by the British Acupuncture Council who state that it aims to “help better inform people about the ancient practice of traditional acupuncture. With 2.3 million acupuncture treatments carried out each year, acupuncture is one of the most popular complementary therapies practised in the UK today.

Right, let’s inform people about acupuncture then! Let’s show them that there is often more to acupuncture research than meets the eye.

My team and I have done lots of research into acupuncture and probably published more papers on this than any other subject. We had prominent acupuncturists on board from the UK, Korea, China and Japan, we ran conferences, published books and are proud to have been innovative and productive in our multidisciplinary research. But here I do not intend to dwell on our own achievements, rather I will highlight several important new papers in this area.

Korean authors just published a meta-analysis to assess the effectiveness of acupuncture as  therapy for gouty arthritis. Ten RCTs involving 852 gouty arthritis patients were included. Six studies of 512 patients reported a significant decrease in uric acid in the treatment group compared with a control group, while two studies of 120 patients reported no such effect. The remaining four studies of 380 patients reported a significant decrease in pain in the treatment group.

The authors conclude “that acupuncture is efficacious as complementary therapy for gouty arthritis patients”.

We should be delighted with such a positive and neat result! Why then do I hesitate and have doubts?

I believe that this paper reveals several important issues in relation to systematic reviews of Chinese acupuncture trials and studies of other TCM interventions. In fact, this is my main reason for discussing the new meta-analysis here. The following three points are crucial, in my view:

1) All the primary studies were from China, and 8 of the 10 were only available in Chinese.

2) All of them had major methodological flaws.

3) It has been shown repeatedly that all acupuncture-trials from China are positive.

Given this situation, the conclusions of any review for which there are only Chinese acupuncture studies might as well be written before the actual research has started. If the authors are pro-acupuncture, as the ones of the present article clearly are, they will conclude that “acupuncture is efficacious“. If the research team has some critical thinkers on board, the same evidence will lead to an entirely different conclusion, such as “due to the lack of rigorous trials, the evidence is less than compelling.

Systematic reviews are supposed to be the best type of evidence we currently have; they are supposed to guide therapeutic decisions. I find it unacceptable that one and the same set of data could be systematically analysed to generate such dramatically different outcomes. This is confusing and counter-productive!

So what is there to do? How can we prevent being misled by such articles? I think that medical journals should refuse to publish systematic reviews which so clearly lack sufficient critical input. I also believe that reviewers of predominantly Chinese studies should provide English translations of these texts so that they can be independently assessed by those who are not able to read Chinese – and for the sake of transparency, journal editors should insist on this point.

And what about the value of acupuncture for gouty arthritis? I think I let the readers draw their own conclusion.

Everyone knows, I think, that smoking is bad for our health. Why then do so many of us still smoke? Because smoking is addictive – and addictions are, by definition, far from easy to get rid of. Many smokers try acupuncture, and acupuncturists are making a ‘pretty penny’ on the assumption that  their treatment is an effective way to stop the habit. But what does the best evidence tell us?

A new randomized, double-blind, placebo-controlled clinical trial with 125 smokers was conducted to determine whether ear acupuncture with electrical stimulation (auriculotherapy) once a week for 5 consecutive weeks is more effective than sham treatment.

The results showed that there was no difference in the rate of smoking cessation between the two groups. After 6 weeks, the auriculotherapy group achieved a rate of 20.9% abstinence which was not significantly different from the 17.9% in the sham group.

The authors  of this study concluded that “the results … do not support the use of auriculotherapy to assist with smoking  cessation. It is possible that a longer treatment duration, more frequent sessions, or other modifications of the intervention       protocol used in this study may result in a different outcome. However, based on the results of this study, there is no evidence that auriculotherapy is superior to placebo when offered once a week for 5 weeks, as described in previous uncontrolled studies.”

Of course, they are correct to state that, theoretically, a different treatment regimen might have generated different outcomes. But how likely is that in reality?

To answer this question, we might consult the Cochrane review on the subject (which incidentally is close to my heart: I initiated it many years ago and was its senior author until it was plagiarised by my former co-worker and my name was replaced by that of his new boss [never a dull day in alternative medicine research!]).

The latest version of this article concludes that “there is no consistent, bias-free evidence that acupuncture, acupressure, laser therapy or electrostimulation are effective for smoking cessation, but lack of evidence and methodological problems mean that no firm conclusions can be drawn. Further, well designed research into acupuncture, acupressure and laser stimulation is justified since these are popular interventions and safe when correctly applied, though these interventions alone are likely to be less effective than evidence-based interventions

This is a very, very (yes, I meant very, very) odd conclusion, I think. If I had still been an author of this plagiarised paper, I would have suggested something a little more straightforward: 33 studies of various types of acupuncture for smoking cessation are currently available (if we include the new trial, the number is 34). The totality of this evidence fails to show that acupuncture is effective. Therefore acupuncture should NOT be considered a valid option for this indication.

Since weeks I have been searching for new (2013) studies which actually report POSITIVE results. I like good news as much as the next man but, in my line of business, it seems awfully hard to come by. Therefore I am all the more delighted to present these two new articles to my readers.

The first study is a randomized trial with patients suffering from metastatic cancer who received one of three interventions: massage therapy, no-touch intervention or usual care. Primary outcomes were pain, anxiety, and alertness; secondary outcomes were quality of life and sleep. The mean number of massage therapy sessions per patient was 2.8.

The results show significant improvement in the quality of life of the patients who received massage therapy after 1-week follow-up which was not observed in either of the other groups. Unfortunately, the difference was not sustained at 1 month. There were also trends towards improvement in pain and sleep of the patients after massage. No serious adverse events were noted.

The authors conclude that “providing therapeutic massage improves the quality of life at the end of life for patients and may be associated with further beneficial effects, such as improvement in pain and sleep quality. Larger randomized controlled trials are needed to substantiate these findings“.

The second study examined the effectiveness of a back massage for improving sleep quality in 60 postpartum women suffering from poor sleep. They were  randomized to either the intervention or the control group. Participants in both groups received the same care except for the back massages. The intervention group received one 20-minutes back massage at the same time each evening for 5 consecutive days by a certified massage therapist. The outcome measure was the Pittsburgh Sleep Quality Index (PSQI). The results showed that the changes in mean PSQI were significantly lower in the intervention group than in controls indicating a positive effect of massage on sleep quality.

The authors’ conclusions were clear: “an intervention involving back massage in the postnatal period significantly improved the quality of sleep.

Where I was trained (Germany), massage is not deemed to be an alternative but an entirely mainstream treatment. Despite this fact, there is precious little evidence to demonstrate that it is effective. Our own research has found encouraging evidence for a range of conditions, including autism, cancer palliation, constipation, DOMS and back pain. In addition, we have shown that massage is not entirely free of risks but that its potential for harm is very low (some might say that this was never in question but it is good to have a bit more solid evidence).

The new studies are, of course, not without flaws; this can hardly be expected in an area where logistical, financial and methodological problems abound. The fact that there are many different approaches to massage does not make things easier either. The new evidence is nevertheless encouraging and seems to suggest that massage has relaxing effects which are clinically relevant. In my view, massage is a therapy worth considering for more rigorous research.

Acupuncture remains a highly controversial treatment: its mechanism of action is less than clear and the clinical results are equally unconvincing. Of course, one ought to differentiate between different conditions; the notion that acupuncture is a panacea is most certainly nonsense.

In many countries, acupuncture is being employed mostly in the management of pain, and it is in this area where the evidence is perhaps most encouraging. Yet, even here the evidence from the most rigorous clinical trials seems to suggest that much, if not all of the effects of acupuncture might be due to placebo.

Moreover, we ought to be careful with generalisations and ask what type of pain? One very specific pain is that caused by aromatase inhibitors (AI), a medication frequently prescribed to women suffering from breast cancer. Around 50 % of these patients complain of AI-associated musculoskeletal symptoms (AIMSS) and 15 % discontinue treatment because of these complaints. So, can acupuncture help these women?

A recent randomised, sham-controlled trial tested whether acupuncture improves AIMSS. Postmenopausal women with early stage breast cancer, experiencing AIMSS were randomized to eight weekly real or sham acupuncture sessions. The investigators evaluated changes in the Health Assessment Questionnaire Disability Index (HAQ-DI) and pain visual analog scale (VAS). Serum estradiol, β-endorphin, and proinflammatory cytokine concentrations were also measured pre and post-intervention. In total, 51 women were enrolled of whom 47 were evaluable (23 randomized to real and 24 to sham acupuncture).

Baseline characteristics turned out to be balanced between groups with the exception of a higher HAQ-DI score in the real acupuncture group. The results failed to show a statistically significant difference in reduction of HAQ-DI or VAS between the two groups. Following eight weekly treatments, a significant reduction of IL-17 was noted in both groups. No significant modulation was seen in estradiol, β-endorphin, or other proinflammatory cytokine concentrations in either group. No difference in AIMSS changes between real and sham acupuncture was seen.

Even though this study was not large, it was rigorously executed and well-reported. As many acupuncturists claim that their treatment alleviates pain and as many women suffering from AM-induced pain experience benefit, acupuncture advocates will nevertheless claim that the findings of this study are wrong, misleading or irrelevant. The often remarkable discrepancy between experience and evidence will again be the subject of intense discussions. How can a tiny trial overturn the experience of so many?

The answer is: VERY EASILY! In fact, the simplest explanation is that both are correct. The trial was well-done and its findings are thus likely to be true. The experience of patients is equally true – yet it relies not on the effects of acupuncture per se, but on the context in which it is given. In simple language, the effects patients experience after acupuncture are due to a placebo-response.

This is the only simple explanation which tallies with both the evidence and the experience. Once we think about it carefully, we realise that acupuncture is highly placebo-genic:

It is exotic.

It is invasive.

It is slightly painful.

It involves time with a therapist.

It involves touch.

If anyone had the task to develop a treatment that maximises placebo-effects, he could not come up with a better intervention!

Ahhh, will acupuncture-fans say, this means that acupuncture is a helpful therapy. I don’t care how it works, as long as it does help. Did we not just cover this issues in some detail? Indeed we did –  and I do not feel like re-visiting the three fallacies which underpin this sentence again.

During the last decade, Professor Claudia Witt and co-workers from the Charite in Berlin have published more studies of homeopathy than any other research group. Much of their conclusions are over-optimistic and worringly uncritical, in my view. Their latest article is on homeopathy as a treatment of eczema. As it happens, I have recently published a systematic review of this subject; it concluded that “the evidence from controlled clinical trials… fails to show that homeopathy is an efficacious treatment for eczema“. The question therefore arises whether the latest publication of the Berlin team changes my conclusion in any way.

Their new article describes a prospective multi-centre study which included 135 children with mild to moderate atopic eczema. The parents of the kids enrolled in this trial were able to choose either homeopathic or conventional doctors for their children who treated them as they saw fit. The article gives only scant details about the actual treatments administered. The main outcome of the study was a validated symptom score at 36 months. Further endpoints included quality of life, conventional medicine consumption, safety and disease related costs at six, 12 and 36 months.

The results showed no significant differences between the groups at 36 months. However, the children treated conventionally seemed to improve quicker than those in the homeopathy group. The total costs were about twice higher in the homoeopathic compared to the conventional group. The authors conclude as follows: “Taking patient preferences into account, while being unable to rule out residual confounding, in this long-term observational study, the effects of homoeopathic treatment were not superior to conventional treatment for children with mild to moderate atopic eczema, but involved higher costs“.

At least one previous report of this study has been available for some time and had thus been included in my systematic review. It is therefore unlikely that this new analysis might change my conclusion, particularly as the trial by Witt et al has many flaws. Here are just some of the most obvious ones:

Patients were selected according to parents’ preferences.

This means expectations could have played an important role.

It also means that the groups were not comparable in various, potentially important prognostic variables.

Even though much of the article reads as though the homeopaths exclusively employed homeopathic remedies, the truth is that both groups received similar amounts of conventional care and treatments. In other words, the study followed a ‘A+B versus B’ design (here is the sentence that best gives the game away “At 36 months the frequency of daily basic skin care was… comparable in both groups, as was the number of different medications (including corticosteroids and antihistamines)…”). I have previously stated that this type of study-design can never produce a negative result because A+B is always more than B.

Yet, at first glance, this new study seems to prove my thesis wrong: even though the parents chose their preferred options, and even though all patients were treated conventionally, the addition of homeopathy to conventional care failed to produce a better clinical outcome. On the contrary, the homeopathically treated kids had to wait longer for their symptoms to ease. The only significant difference was that the addition of homeopathy to conventional eczema treatments was much more expensive than conventional therapy alone (this finding is less than remarkable: even the most useless additional intervention costs money).

So, is my theory about ‘A+B versusB’ study-designs wrong? I don’t think so. If B equals zero, one would expect exactly the finding Witt et al produced:  A+0=A. In turn, this is not a compliment for the homeopaths of this study: they seem to have been incapable of even generating a placebo-response. And this might indicate that homeopathy was not even usefull as a means to generate a placebo-response. Whatever interpretation one adopts, this study tells us very little of value (as children often grow out of eczema, we cannot even be sure whether the results are not simply a reflection of the natural history of the disease); in my view, it merely demonstrates that weak study designs can only create weak findings which, in this particular case, are next to useless.

The study was sponsored by the Robert Bosch Stiftung, an organisation which claims to be dedicated to excellence in research and which has, in the past, spent millions on researching homeopathy. It seems doubtful that trials of this caliber can live up to any claim of excellence. In any case, the new analysis is certainly no reason to change the conclusion of my systematic review.

To their credit, Witt et al are well aware of the many weaknesses of their study. Perhaps in an attempt to make them appear less glaring, they stress that “the aim of this study was to reflect the real world situation“.Usually I do not accept the argument that pragmatic trials cannot be rigorous – but I think Witt et al do have a point here: the real word tells us that homeopathic remedies are pure placebos!

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