MD, PhD, FMedSci, FSB, FRCP, FRCPEd

Chinese studies

The news that the use of Traditional Chinese Medicine (TCM) positively affects cancer survival might come as a surprise to many readers of this blog; but this is exactly what recent research has suggested. As it was published in one of the leading cancer journals, we should be able to trust the findings – or shouldn’t we?

The authors of this new study used the Taiwan National Health Insurance Research Database to conduct a retrospective population-based cohort study of patients with advanced breast cancer between 2001 and 2010. The patients were separated into TCM users and non-users, and the association between the use of TCM and patient survival was determined.

A total of 729 patients with advanced breast cancer receiving taxanes were included. Their mean age was 52.0 years; 115 patients were TCM users (15.8%) and 614 patients were TCM non-users. The mean follow-up was 2.8 years, with 277 deaths reported to occur during the 10-year period. Multivariate analysis demonstrated that, compared with non-users, the use of TCM was associated with a significantly decreased risk of all-cause mortality (adjusted hazards ratio [HR], 0.55 [95% confidence interval, 0.33-0.90] for TCM use of 30-180 days; adjusted HR, 0.46 [95% confidence interval, 0.27-0.78] for TCM use of > 180 days). Among the frequently used TCMs, those found to be most effective (lowest HRs) in reducing mortality were Bai Hua She She Cao, Ban Zhi Lian, and Huang Qi.

The authors of this paper are initially quite cautious and use adequate terminology when they write that TCM-use was associated with increased survival. But then they seem to get carried away by their enthusiasm and even name the TCM drugs which they thought were most effective in prolonging cancer survival. It is obvious that such causal extrapolations are well out of line with the evidence they produced (oh, how I wished that journal editors would finally wake up to such misleading language!) .

Of course, it is possible that some TCM drugs are effective cancer cures – but the data presented here certainly do NOT demonstrate anything like such an effect. And before such a far-reaching claim is being made, much more and much better research would be necessary.

The thing is, there are many alternative and plausible explanations for the observed phenomenon. For instance, it is conceivable that users and non-users of TCM in this study differed in many ways other than their medication, e.g. severity of cancer, adherence to conventional therapies, life-style, etc. And even if the researchers have used clever statistical methods to control for some of these variables, residual confounding can never be ruled out in such case-control studies.

Correlation is not causation, they say. Neglect of this elementary axiom makes for very poor science – in fact, it produces dangerous pseudoscience which could, like in the present case, lead a cancer patient straight up the garden path towards a premature death.

Alternative medicine thrives in the realm of common chronic conditions which conventional medicine cannot cure and which respond well to treatment with placebos. Irritable bowel syndrome (IBS) is such a condition, and IBS-sufferers who are often frustrated with the symptomatic relief conventional medicine has to offer are only too keen to try any therapy that promises help. There is hardly an alternative therapy which does not claim to be the solution to IBS-symptoms: herbal medicine, mind-body interventions, homeopathy (the subject of my next post), acupuncture, even ‘MOXIBUSTION‘.

Moxibustion is a derivative of acupuncture; instead of needles, this method employs heat to stimulate acupuncture points. Proponents believe that the effects of moxibustion are roughly equivalent to those of acupuncture but many acupuncturists feel that they are less powerful. One website explains: Moxibustion is a traditional Chinese medicine technique that involves the burning of mugwort, a small, spongy herb, to facilitate healing. Moxibustion has been used throughout Asia for thousands of years; in fact, the actual Chinese character for acupuncture, translated literally, means “acupuncture-moxibustion.” The purpose of moxibustion, as with most forms of traditional Chinese medicine, is to strengthen the blood, stimulate the flow of qi, and maintain general health.

Many proponents of moxibustion claim that their treatment works for IBS. The evidence is, however, far less clear. Two recent meta-analyses might tell us more.

The first systematic review and meta-analysis was published by Korean researchers and aimed at critically evaluating the current evidence on moxibustion for improving global symptoms of IBS. The authors conducted extensive searches and found a total of 20 RCTs to be included in their analyses. The risk of bias in these studies was generally high. Compared with pharmacological medications, moxibustion significantly alleviated overall IBS symptoms but there was a moderate inconsistency among the 7 RCTs. Moxibustion combined with acupuncture was more effective than pharmacological therapy but a moderate inconsistency among the 4 studies was found. When moxibustion was added to pharmacological medications or herbal medicine, no additive benefit of moxibustion was shown compared with pharmacological medications or herbal medicine alone. One small sham-controlled trial found no difference between moxibustion and sham control in symptom severity. Moxibustion appeared to be associated with few adverse events but the evidence is limited due to poor reporting.

The authors concluded that moxibustion may provide benefit to IBS patients although the risk of bias in the included studies is relatively high. Future studies are necessary to confirm whether this finding is reproducible in carefully-designed and conducted trials and to firmly establish the place of moxibustion in current practice.

The way I see it, these conclusions are far too optimistic. There was only one RCT that controlled for placebo-effects, and the results of that study were negative. Thus I would conclude that some studies report effectiveness of moxibustion for IBS, yet the effects seem not to be caused by the treatment per se but are most likely due to a placebo-effect.

The second systematic review and meta-analysis was published by Chinese researchers and aimed at evaluating the clinical efficacy and safety of moxibustion and acupuncture in treatment of IBS. The authors included randomized and quasi-randomized clinical trials in their analyses and were able to include 11 trials. Their meta analysis suggests that the effectiveness of the combined methods of acupuncture and moxibustion is superior to conventional western medication treatment. The authors concluded that acupuncture-moxibustion for IBS is better than the conventional western medication treatment.

While the first meta-analysis was at least technically sound, the second seems to have too many flaws to mention: the search methodology was flimsy, many available studies were not included, their risk of bias was not assessed critically, the conclusions are based more on wishful thinking than on the available data, etc.

If we consider that moxibustion is a method of stimulating acupoints, we have to assume that it can at best be as effective as acupuncture, quite possibly slightly less. Thus it is relevant to see what the evidence tells us about acupuncture for IBS. The current Cochrane review of acupuncture for IBS shows that sham-controlled RCTs have found no benefits of acupuncture relative to a credible sham acupuncture control for IBS symptom severity or IBS-related quality of life.

I think I rest my case.

This post has an odd title and addresses an odd subject. I am sure some people reading it will ask themselves “has he finally gone potty; is he a bit xenophobic, chauvinistic, or what?” I can assure you none of the above is the case.

Since many years, I have been asked to peer-review Chinese systematic reviews and meta-analyses of TCM-trials submitted to various journals and to the Cochrane Collaboration for publication, and I estimate that around 300 such articles are available today. Initially, I thought they were a valuable contribution to our knowledge, particularly for the many of us who cannot read Chinese languages. I hoped they might provide reliable information about this huge and potentially important section of the TCM-evidence. After doing this type of work for some time, I became more and more frustrated; now I have decided not to accept this task any longer – not because it is too much trouble, but because I have come to the conclusion that these articles are far less helpful than I had once assumed; in fact, I now fear that they are counter-productive.

In order to better understand what I mean, it might be best to use an example; this recent systematic review seems as good for that purpose as any.

Its Chinese authors “hypothesized that the eligible trials would provide evidence of the effect of Chinese herbs on bone mineral density (BMD) and the therapeutic benefits of Chinese medicine treatment in patients with bone loss. Randomized controlled trials (RCTs) were thus retrieved for a systematic review from Medline and 8 Chinese databases. The authors identified 12 RCTs involving a total of 1816 patients. The studies compared Chinese herbs with placebo or standard anti-osteoporotic therapy. The pooled data from these RCTs showed that the change of BMD in the spine was more pronounced with Chinese herbs compared to the effects noted with placebo. Also, in the femoral neck, Chinese herbs generated significantly higher increments of BMD compared to placebo. Compared to conventional anti-osteoporotic drugs, Chinese herbs generated greater BMD changes.

In their abstract, the part on the paper that most readers access, the authors reached the following conclusions: “Our results demonstrated that Chinese herb significantly increased lumbar spine BMD as compared to the placebo or other standard anti-osteoporotic drugs.” In the article itself, we find this more detailed conclusion: “We conclude that Chinese herbs substantially increased BMD of the lumbar spine compared to placebo or anti-osteoporotic drugs as indicated in the current clinical reports on osteoporosis treatment. Long term of Chinese herbs over 12 months of treatment duration may increase BMD in the hip more effectively. However, further studies are needed to corroborate the positive effect of increasing the duration of Chinese herbs on outcome as the results in this analysis are based on indirect comparisons. To date there are no studies available that compare Chinese herbs, Chinese herbs plus anti-osteoporotic drugs, and anti-osteoporotic drug versus placebo in a factorial design. Consequently, we are unable to draw any conclusions on the possible superiority of Chinese herbs plus anti-osteoporotic drug versus anti-osteoporotic drug or Chinese herb alone in the context of BMD.

Most readers will feel that this evidence is quite impressive and amazingly solid; they might therefore advocate routinely using Chinese herbs for the common and difficult to treat problem of osteoporosis. The integration of TCM might avoid lots of human suffering, prolong the life of many elderly patients, and save us all a lot of money. Why then am I not at all convinced?

The first thing to notice is the fact that we do not really know which of the ~7000 different Chinese herbs should be used. The article tells us surprisingly little about this crucial point. And even, if we manage to study this question in more depth, we are bound to get thoroughly confused; there are simply too many herbal mixtures and patent medicines to easily identify the most promising candidates.

The second and more important hurdle to making sense of these data is the fact that most of the primary studies originate from inaccessible Chinese journals and were published in Chinese languages which, of course, few people in the West can understand. This is entirely our fault, some might argue, but it does mean that we have to believe the authors, take their words at face value, and cannot check the original data. You may think this is fine, after all, the paper has gone through a rigorous peer-review process where it has been thoroughly checked by several top experts in the field. This, however, is a fallacy; like you and me, the peer-reviewers might not read Chinese either! (I don’t, and I reviewed quite a few of these papers; in some instances, I even asked for translations of the originals to do the job properly but this request was understandably turned down) In all likelihood, the above paper and most similar articles have not been properly peer-reviewed at all.

The third and perhaps most crucial point can only be fully appreciated, if we were able to access and understand the primary studies; it relates to the quality of the original RCTs summarised in such systematic reviews. The abstract of the present paper tells us nothing at all about this issue. In the paper, however, we do find a formal assessment of the studies’ risk of bias which shows that the quality of the included RCTs was poor to very poor. We also find a short but revealing sentence: “The reports of all trials mentioned randomization, but only seven described the method of randomization.” This remark is much more significant than it may seem: we have shown that such studies use such terminology in a rather adventurous way; reviewing about 2000 of these allegedly randomised trials, we found that many Chinese authors call a trial “randomised” even in the absence of a control group (one cannot randomise patients and have no control group)! They seem to like the term because it is fashionable and makes publication of their work easier. We thus have good reason to fear that some/many/most of the studies were not RCTs at all.

The fourth issue that needs mentioning is the fact that very close to 100% of all Chinese TCM-trials report positive findings. This means that either TCM is effective for every indication it is tested for (most unlikely, not least because there are many negative non-Chinese trials of TCM), or there is something very fundamentally wrong with Chinese research into TCM. Over the years, I have had several Chinese co-workers in my team and was invariably impressed by their ability to work hard and efficiently; we often discussed the possible reasons for the extraordinary phenomenon of 0% negative Chinese trials. The most plausible answer they offered was this: it would be most impolite for a Chinese researcher to produce findings which contradict the opinion of his/her peers.

In view of these concerns, can we trust the conclusions of such systematic reviews? I don’t think so – and this is why I have problems with research of this nature. If there are good reasons to doubt their conclusions, these reviews might misinform us systematically, they might not further but hinder progress, and they might send us up the garden path. This could well be in the commercial interest of the Chinese multi-billion dollar TCM-industry, but it would certainly not be in the interest of patients and good health care.

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.

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