A review or three from 2019

Stimulated by three review papers appearing on PubMed in the last week of 2019.[1–3]

This time of year is ripe with reviews… usually the past year on broadcast media rather than research reviews, as I have chosen here. They are all quite different and I aim to highlight different aspects in each of them.

…weak at the knees?

If you are feeling a little weak at the knees after a long night of seeing in 2020 (well you probably won’t be seeing 2020 for a while yet, and probably not reading this blog either), the first review might give you a little strength, or the hope of achieving some. It is a review of the effectiveness and safety of acupuncture in myasthenia gravis.[1] The review authors are from the China Academy of Chinese Medical Sciences, and all the RCTs included were from China (RCTs 13; total participants 775), published in Chinese journals and written in Chinese. You can see how useful it might be to have some Chinese language authors on the team when performing systematic reviews of acupuncture. If you did the same review limited to English you would have nothing to include!

Most of the trials used acupuncture in addition to pyridostigmine and steroids, although one or two used herbal medicine rather than the steroids. This seems like a sensible approach to me considering the nature of the condition. I was pleased to see lots of red and yellow colours in the RoB (risk of bias) summary figure, reflecting a lack of blinding, although perhaps there should have been even more red!

…even more red!

The forest plots show a small effect of additional acupuncture that just reaches statistical significance in both relative and absolute clinical scores. It is interesting to note that when trials are subdivided into those with 8 or fewer weeks treatment and 12 or more weeks treatment, there is only a significant effect associated with the longer treatment course.

The second review I noticed was on acupuncture versus drugs in migraine prevention.[2] Another lead author with the name Zhang led me to assume I was going to see another review of principally Chinese literature, but no, these authors are based in the US. They are from Stanford and Harvard no less. But wait, the last author actually works for Big Pharma! This was suddenly more intriguing…

The review was limited to the English literature, despite the first author’s surname. It included only 7 studies, and there was no attempt to pool any data. Having said that, it was published in a high-profile journal, and had a fairly positive conclusion:

There is growing evidence that acupuncture is just as effective and has fewer side effects than many of the standard pharmaceutical agents that are currently used.

Zhang et al Headache 2019 [2]

Only one study was not included (or excluded) from the Cochrane Review of 2016,[4] and that was published in 2017.[5] It was a moderately large (n=150) 3 arm trial based in Iran comparing acupuncture, botulinum toxin A and sodium valproate. Acupuncture came out on top by quite a margin, but the patients did receive a lot of treatment – 30 sessions in 60 days.

I’m still intrigued by the industry affiliation of the last author… I wonder if she still has a job after publishing this review?

I wonder if she still has a job…

I must stop being so cynical… is that a potential resolution for 2020? Not when it comes to Big Pharma I think!

On to the third review, and this was a review of systematic reviews (SRs) of acupuncture in chronic pain, with familiar authors in a relatively unfamiliar journal (at least to me). It is open access, so I clicked through to find it was a massive piece of work including 177 SRs spanning 30 years (1989 to 2019 ie most of my career). The pdf version of this paper runs to 62 pages, and more than half of those (pages 5–43) are covered with tabular summaries of the included SRs. There follows a narrative summary by categories, and a discussion of the challenges of acupuncture research (sample sizes, controls and adequacy of dose).

This is certainly a useful paper for anyone writing a long case for their acupuncture diploma, with its 225 references, and well-structured layout.

EERW – Enriched Enrolment Randomised Withdrawal

The final section discusses design of future RCTs and introduces the idea of adopting the EERW approach for acupuncture research. EERW stands for Enriched Enrolment Randomised Withdrawal – a strategy developed by the pharmaceutical industry to get the best results for drugs that are poorly tolerated by a relatively large percentage of patients (ie most drugs in chronic pain). Patients are taken off their existing medication and started on the active drug. Those that tolerate the drug and appear to respond are then enrolled and randomised to either continuing on the drug (after a brief period of weaning off) or transferring onto a placebo (after a similar period of weaning off the active drug). This approach maximises the potential measurement of efficacy over placebo but underestimates the adverse effect profile since those most sensitive to these effects dropout before enrolment.

I thought about this design some years ago, when it first became popular in pharmaceutical research, but I fear there are all manner of potential problems if we substitute acupuncture in place of a pill. I like the idea of enriched enrolment, so we only test those that we know respond to acupuncture but blinding of patients may become more difficult with this design as they are all no longer naïve to the technique at the point of enrolment. A further worry is that the run-in period of real treatment could condition an enhanced response to a sham technique in some patients and have a long-term therapeutic effect on others (for example the effect of a course of acupuncture in chronic headache can last over a year).

I would be cautious…

In summary, I would be cautious about adopting EERW, and I would still favour electroacupuncture versus non penetrating sham in most chronic pain conditions (not headache) if we need to continue efficacy trials at all.

References

1         Zhang X, Ding W, Wang Z, et al. The effectiveness and safety of acupuncture for the treatment of myasthenia gravis: a systematic review and meta-analysis of randomized controlled trials. Ann Palliat Med 2019;8:576–85. doi:10.21037/apm.2019.10.10

2         Zhang N, Houle T, Hindiyeh N, et al. Systematic Review: Acupuncture vs Standard Pharmacological Therapy for Migraine Prevention. Headache Published Online First: 24 December 2019. doi:10.1111/head.13723

3         Paley CA, Johnson MI. Acupuncture for the Relief of Chronic Pain: A Synthesis of Systematic Reviews. Medicina (Kaunas) 2019;56:6. doi:10.3390/medicina56010006

4         Linde K, Allais G, Brinkhaus B, et al. Acupuncture for the prevention of episodic migraine. Cochrane database Syst Rev 2016;:CD001218. doi:10.1002/14651858.CD001218.pub3

5         Naderinabi B, Saberi A, Hashemi M, et al. Acupuncture and botulinum toxin A injection in the treatment of chronic migraine: A randomized controlled study. Casp J Intern Med 2017;8:196–204. doi:10.22088/cjim.8.3.196

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Declaration of interests MC